Dopamine System

Brain monoamines (serotonin, norepinephrine, dopamine, and histamine) play an important role in emotions, cognition and in pathophysiology and treatment of mental disorders. The interactions between serotonin, norepinephrine and dopamine were studied in numerous works, however, histamine system received less attention. The aim of this study was to investigate the interactions between histamine and other monoamines, using in vivo microdialys and electrophysiology. It was found that the inverse agonist of histamine-3 receptors, thioperamide, increased the firing activity of dopamine neurons in the ventral tegmental area. Selective agonist of histamine-3 receptors, immepip, reversed thiperamide-induced stimulation of firing activity of dopamine neurons. The firing rates of serotonin and norepinephrine neurons were not attenuated by immepip or thioperamide. Thioperamide robustly and significantly increased extracellular concentrations of serotonin, norepinephrine, and dopamine in the rat prefrontal cortex and slightly increased norepinephrine and dopamine levels in the tuberomammillary nucleus of the hypothalamus. It can be concluded that histamine stimulates serotonin, norepinephrine, and dopamine transmission in the brain. Modulation of firing of dopamine neurons is a key element in functional interactions between histamine and other monoamines. Antagonists of histamine-3 receptors, because of their potential ability to stimulate monoamine neurotransmission, might be beneficial in the treatment of mental disorders.

An influential theory within personality neuroscience suggests that trait extraversion is underpinned by individual differences in dopamine function. In a review of the relevant literature, we evaluate this theory in light of the evidence from molecular genetics, neuroimaging, and psychopharmacology. Evidence linking individual differences in extraversion with dopamine-relevant genes, structural volume of dopamine-rich brain regions (e.g., in striatal and ventral prefrontal areas), dopamine receptor availability, and frontal alpha asymmetry is mixed at best. Evidence concerning both scalp recorded (electroencephalogram) and hemodynamic (functional magnetic resonance imaging) neural responses to rewards appears somewhat more promising. Perhaps the best evidence concerns extraversion- dependent responses – both neural and behavioural – to dopaminergic drugs. Future research in this area must go beyond the demonstration of theoretically consistent associations and attempt to provide more specific causal evidence for the dopamine hypothesis of extraversion. A further challenge is to expand this hypothesis to incorporate other neurobiological processes that are likely to underlie this trait.

Abstract: There are twelve major acupuncture meridians. Each one is associated with a color, an element and so much more. In Traditional Chinese Medicine, each acupuncture / acupressure meridian is associated with sensations and other aspects of health and healing. For example the Gallbladder meridian is associated with the color green. Emotional Freedom Technique or EFT Tapping points are also associated with the reflex points of certain meridians. For example, the side of the eye tapping point is the beginning of the gallbladder meridian.
Following in the footsteps of Harvard researcher, Amy Cuddy, who found associations between different body postures (Wonder Woman Pose) and hormones and neurotransmitters (cortisol and testosterone), this research postulates associations between different meridians and neurotransmitters as well as the corresponding EFT points. For example, dopamine is associated with the gallbladder meridian and a posture or movement known as long walking. This information can be used in giving clients self-care exercises and visualizations, including motor imagery, guided imagery, and visualizations based on the function of mirror neurons. From a presentation on May 18, 2013. Kimberly Burnham, PhD, The Nerve Whisperer spoke on "Colors, Acupuncture Meridians, EFT Points, and Brain Chemistry" at the Spring Energy EFT TapFest in New York, Your Globally Conscious Tapping Community.

There is also a radio show associated with this presentation: "Every Cell is Listening: So What Are You Saying? Hearing?" on EFT Radio Jondi Whitis on Blog Talk Radio http://www.blogtalkradio.com/eftradio/2012/12/21/brain-health-tap-into-information-medecine

Burnham, Kimberly (2013 05 18). Colors, Acupuncture Meridians, EFT Points, and Brain Chemistry Spring Energy EFT TapFest [Full Text] https://www.academia.edu/17535615/Colors_Acupuncture_Meridians_EFT_Points_and_Brain_Chemistry

This paper presents a model of Asperger Syndrome as a hypodopaminergic condition. Several genetic factors lead to a faster than normal turnover of dopamine and chronically low dopaminergic tone reminiscent of pre-clinical Parkinson’s Disease. It explores three etiologies from different genetic bases, leading to similar hypodopaminergic states:

1. Dopamine Transporter type (DAT type): Polymorphisms in SLC6A3 causing dopamine leakage from the DAT, the 10-repeat VNTR of SLC6A3 causing DAT overexpression, or syntaxin 1A polymorphisms leading to increased DAT function and a faster rate of dopamine turnover: ‘the overclocking model’. The subsequent postsynaptic low dopaminergic tone may cause higher neuronal excitability and a faster rate of firing, producing sensory hypersensitivity, fast thoughts, sensitivity to salience, poor executive function and anxiety.

2. Glutamate type: Polymorphisms of SLC25A12 resulting in a reduction of VMAT2 and dysfunctional dopamine handling and oxidative stress within the neuron.

3. GABRB3 type: Polymorphisms of GABRB3 causing reduced binding to GABAA receptors with a β3 subunit. GABAA receptors co-localise with dopamine D2 receptors, and levels of tonic dopamine may modulate them in terms of neuronal spine formation. Reduced β3 subunit function/expression may inhibit the emission of more dopamine, leading to chronically low dopamine.

The paper discusses compounding effects from stress hormones and COMT. It describes the ‘female protective effects’ and male exacerbative effects of sex hormones on tonic dopamine levels.

Viewing Asperger Syndrome as a dopaminergic disorder allows us to develop a diagnostic tool focusing on hypodopaminergic traits. It also opens an avenue of research into treatment with modafinil, a dopamine reuptake inhibitor, for AS depression, self-harm and suicidality.

Research has shown that the brain is constantly making predictions about future events. Theories of prediction in perception, action and learning suggest that the brain serves to reduce the discrepancies between expectation and actual experience, i.e., by reducing the prediction error. Forward models of action and perception propose the generation of a predictive internal representation of the expected sensory outcome, which is matched to the actual sensory feedback. Shared neural representations have been found when experiencing one's own and observing other's actions, rewards, errors, and emotions such as fear and pain. These general principles of the "predictive brain" are well established and have already begun to be applied to social aspects of cognition. The application and relevance of these predictive principles to social cognition are discussed in this article. Evidence is presented to argue that simple non-social cognitive processes can be extended to explain complex cognitive processes required for social interaction, with common neural activity seen for both social and non-social cognitions. A number of studies are included which demonstrate that bottom-up sensory input and top-down expectancies can be modulated by social information. The concept of competing social forward models and a partially distinct category of social prediction errors are introduced. The evolutionary implications of a "social predictive brain" are also mentioned, along with the implications on psychopathology. The review presents a number of testable hypotheses and novel comparisons that aim to stimulate further discussion and integration between currently disparate fields of research, with regard to computational models, behavioral and neurophysiological data. This promotes a relatively new platform for inquiry in social neuroscience with implications in social learning, theory of mind, empathy, the evolution of the social brain, and potential strategies for treating social cognitive deficits.

Behavioral genetic studies had examined whether the genetic basis had an influence on antisocial behaviors, they revealed that the violent criminal behavior arising from the interaction between several genetics and environmental factors .The present study reflect the role of polymorphisms in Catechol-O-methyl transferase (comt) gene on violent criminal behavior in Iraqi prisoners. Methods: blood samples were collected from 200 prisoners (case group) who convicted with terrorism (150 sample), murder(30 sample) and drug trading (20 sample) issues selected from Al –Hila prison reformist central for men and women / Babylon city and from position and deporting division /Karbala ,this sample include (160 male and 40 female).Additionally, 100 sample were collected as control groups included (54 male and 46 female). DNA was extracted from the peripheral blood of all participants, and the above mentioned single-nucleotide polymorphisms (SNPs) were genotyped by RFLP-PCR(Restriction Fragment Length Polymorphism). The results were confirmed by using sequencing technique. Results: The result of the RFLP PCR and DNA sequencing methods for comt (Val 158 Met) polymorphism revealed that the homo-mutant genotype A/A(Met/Met) have significant higher risk of criminal behavior (p= 0.001 ;OR= 3.98 ; 95% CI= 1.7-9.3) when compared with control and the A allele (Met allele) frequency was a significant associated with case group (p=0.003; OR= 1.68; 95%CI= 1.19-2.37). Conclusion: the presence of the Met allele of the comt gene results in a significant increase in the risk of the susceptibility of individual to engage in to crimes in the presence of certain environment risk factors.

Efek samping parkinsonisme merupakan suatu bagian dari sindrom ekstrapiramidal yang muncul akibat penggunaan antipsikotik. Skizofrenia merupakan gangguan jiwa berat yang ditandai oleh dua atau lebih tanda tanda halusinasi, pembicaraan tidak teratur, sikap katakonik, emosi negatif seperti kehilangan ekspresi emosi. Gangguan di jaras nigrostriatal oleh penggunaan antipsikotik dapat mencetus timbulnya efek samping parkinsonisme pada pasien skizofrenia. Pola penggunaan antipsikotik, antipsikotik tipikal ataupun antipsikotik yang melebihi dosis dapat menimbulkan efek samping parkinonisme. Tujuan dari penelitian ini adalah untuk mengetahui hubungan antara pola pemberian obat antipsikotik terhadap efek samping parkinsonisme pada pasien skizofrenia di Badan Layanan Umum Daerah Rumah Sakit Jiwa Aceh tahun 2015. Pengambilan sampel menggunakan teknik accidental sampling dengan jumlah sampel 501 pasien yang terdiri atas 222 pasien dengan pola pengobatan monoterapi dan 279 pasien dengan pola pengobatan polifarmaka. Pengumpulan data dilakukan melalui rekam medik pasien. Hasil penelitian menunjukkan jumlah pasien dengan efek samping parkinsonisme adalah 258 orang (51,5%). Jenis antipsikotik yang paling banyak diberikan adalah kombinasi antipsikotik atipikal berjumlah 108 (37,3%). Pola pengobatan yang mendominasi pasien dengan efek samping parkinsonisme adalah polifarmaka sebanyak 152 (59%). Jenis kelamin pasien dengan efek samping parkinsonisme paling banyak ditemukan adalah laki laki dengan jumlah 204 pasien (79%). Kelompok usia yang paling banyak ditemukan pada pasien dengan efek samping parkinsonisme adalah 25-45 tahun dengan jumlah 179 pasien (69,4%). Hasil analisis dengan metode chi-square menunjukkan adanya hubungan pola pemberian obat antipsikotik terhadap efek samping parkinsonisme pada pasien skizofrenia dengan nilai signifikansi 0,010 (p <0,05).



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ABSTRACT
Drug induced-parkinsonism (DIP) is part of extrapyramidal syndrome which is caused by the use of antipsychotic. Schizophrenia is a severe mental condition signified by two or more signs of hallucination dissociated conversation, catatonic, and negative emotions such as loss of expression. Disturbance in nigrostriatal pathway by antipsychotic usage may cause DIP on schizophrenic patients. Antipsychotic usage  pattern, typical antipsychotic, or overdosing of antipsychotic may cause DIP. The  purpose of this research is to analyze the association between antipsychotic usage  pattern and DIP on schizophrenic patients in General Regional Service Unit of Aceh  Mental Health Hospital on 2015. Samples were obtained by using accidental sampling method with total sample of 501 patients analyzed of which 222 patients using monotherapy antipsychotic usage pattern and 279 patients using polypharmacy antipsychotic usage pattern. Data was obtained via medical record. The result of this research shows the total of patient with DIP was 258 patients (51,5%). Most given type of antipsychotic is atypical with total of 108 (37,3%). Antipsychotic usage pattern which is dominating the patients with DIP was polypharmacy with total of 152 (59%). Most  found gender in patients with DIP was male with total of 204 patients (79%). Most  patients were in age group of 25-45 with total of 179 patients (69,4%). Analysis with chi-square shows that there is association between antipsychotic usage pattern with  DIP on schizophrenic patients with significance value of 0,010 (p <0,05)

Recent work using the eye movement monitoring technique has demonstrated that when people are engaged in thought they tend to disengage from the external world by blinking or fixating on an empty portion of the visual field, such as a blank wall, or out the window at the sky. This ‘looking at nothing’ behavior has been observed during thinking that does not explicitly involve visual imagery (mind wandering, insight in problem solving, memory encoding and search) and it is associated with reduced analysis of the external visual environment. Thus, it appears to indicate (and likely facilitate) a shift of attention from external to internal stimuli that benefits creativity and problem solving by reducing the cognitive load and enhancing attention to internally evolving activation. We briefly mention some possible reasons to collect eye movement data in future studies of creativity.

ABSTRACT: This chapter argues that appeals to actual scientific practice show that higher-level psychological explanations are not precluded by reductive explanation, much less rendered extinct. To exemplify this conclusion, the case of mesocorticolimbic dopamine is discussed at length.

ABSTRACT: Courtesy of its free energy formulation, the hierarchical predictive processing theory of the brain is often claimed to be a grand unifying theory. To test this claim, we consider a central case: reward-related activity of mesocorticolimbic dopaminergic (DA) systems. After reviewing the three most prominent hypotheses of DA activity—the anhedonia, incentive salience, and reward prediction error hypotheses—we conclude that current evidence vindicates explanatory pluralism, while leaves unwarranted the grand unifying claims of the predictive processing theory of the brain. More generally, we suggest that scientific progress in the cognitive sciences is unlikely to come in the form of a single overarching grand unifying theory.

Anticipation and Experience of peak emotion to music : how is it linked to dopamine release ? When thinking about what unconventional non-drug rewarding things are, what usually comes to mind is the biological reinforcers such as eating healthy, drinking well and having sex.

An explorative review of literature of pharmacological aspects of acetylcholine (ACh) and dopamine (DA) neurotransmitter systems on the methods of causation of motor dysfunction, ranging from dyskinesia to tremulous jaw movements. The current author comments on the ACh system with reference to nicotinic ACh receptor (nAChR) blockade, competitive antagonism and tacrine-induced jaw tremor research. The DA system implication is also reviewed and raises current topical issues models of neuro-circuitry and ACh-DA interactions. To conclude, the ACh and DA systems and their interactions require future research to establish concrete mechanisms and the complexities of these system interactions to be explored in relation to dysfunctional motor behaviour.

The past two decades have seen an explosion in our
understanding of the origin and development of the
midbrain dopamine system. Much of this work has
been focused on the aspects of dopamine neuron development
related to the onset of movement disorders
such as Parkinson’s disease, with the intent of hopefully
delaying, preventing or fixing symptoms. While
midbrain dopamine degeneration is a major focus for
treatment and research, many other human disorders
are impacted by abnormal dopamine, including drug
addiction, autism and schizophrenia. Understanding
dopamine neuron ontogeny and how dopamine connections
and circuitry develops may provide us with key
insights into potentially important avenues of research
for other dopamine-related disorders. This review will
provide a brief overview of the major molecular and
genetic players throughout the development of midbrain
dopamine neurons and what we know about the
behavioral- and disease-related implications associated
with perturbations to midbrain dopamine neuron development.
We intend to combine the knowledge of two
broad fields of neuroscience, both developmental and
behavioral, with the intent on fostering greater discussion
between branches of neuroscience in the service of
addressing complex cognitive questions from a developmental
perspective and identifying important gaps in
our knowledge for future study.

doi: 10.1111/gbb.12257

Currentimagingtechniqueshavelimitedabilitytodetectneurotransmittersreleasedduringbrainprocessing.Itisacriticallimitationbecauseneurotransmittershavesignificantcontroloverthebrainactivity.Inthiscontext,recentdevelopmentofsingle-scandynamicmolecularimagingtechniqueisimportantbecauseitallowsdetection,mapping,andmeasurementofdopaminereleasedinthebrainduringtaskperformance.Thetechniqueexploitsthecompetitionbetweenendogenouslyreleaseddopamineanditsreceptorligandforoccupancyofreceptorsites.Dopaminereleasedduringtaskperformanceisdetectedbydynamicallymeasuringconcentrationofintravenouslyinjectedradiolabeledligandusingapositronemissiontomography(PET)camera.Basedontheligandconcentration,valuesofreceptorkineticparametersareestimated.Theseestimatesallowdetectionofdopaminereleasedinthehumanbrainduringtaskperformance.

It is well accepted that a grade shift occurred in hominin evolution approximately 1.9 million years ago with the appearance of Homo erectus. With the challenges of complete terrestrial life, new cognitive abilities were selected for that allowed this species to thrive for the next million and a half years. It has also long been recognized that there was a change in diet with the advent of Homo erectus, that is, a greater reliance on meat. However, the relationship between additional meat and the cognitive abilities of Homo erectus has mostly remained unclear. The present paper proposes that an increase in dietary meat protein and fats may have led to an increase in dopamine and dopaminergic systems, a critical chemical neurotransmitter in the brain. This purported change in dopaminergic systems may have played a key role in many of the traits and abilities exhibited by Homo erectus at that time, including increases in body and brain size, dispersion, and a greater aptitude for spatial and social cognitions.

Objective: To assess the relationship between cognitive function, a proposed schizophrenia
endophenotype, and two genetic polymorphisms related to dopamine function, catechol-O-methyl
transferase (COMT) Val158Met and dopamine receptor 3 (DRD3) Ser9Gly.
Methods: Fifty-eight outpatients with schizophrenia/schizoaffective disorder and 88 healthy controls
underwent neurocognitive testing and genotyping. Analyses of covariance (ANCOVAs) using age, sex,
and years of education as covariates compared cognitive performance for the proposed genotypes in
patients and controls. ANCOVAs also tested for the epistatic effect of COMT and DRD3 genotype
combinations on cognitive performance.
Results: For executive functioning, COMT Val/Val patients performed in a similar range as controls
(30.70-33.26 vs. 35.53-35.67), but as COMT Met allele frequency increased, executive functioning
worsened. COMT Met/Met patients carrying the DRD3 Ser/Ser genotype performed poorest (16.184
vs. 27.388-31.824). Scores of carriers of this COMT/DRD3 combination significantly differed from all
DRD3 Gly/Gly combinations (p o 0.05), from COMT Val/Met DRD3 Ser/Gly (p = 0.02), and from
COMT Val/Val DRD3 Ser/Ser (p = 0.01) in patients. It also differed significantly from all control scores
(p o 0.001).
Conclusion: Combined genetic polymorphisms related to dopamine neurotransmission might
influence executive function in schizophrenia. Looking at the effects of multiple genes on a single
disease trait (epistasis) provides a comprehensive and more reliable way to determine genetic effects
on endophenotypes.

An associative learning task was employed in which, in separate blocks, reinforcement was limited to either correct or incorrect trials. Given the role of dopamine in reinforcement learning, we examined the effects of a dopamine (DA) agonist on performance and obtained genetic information to divide the participants based on two SNPs related to intrinsic DA levels, COMT and DRD2.
Participants learned to associate 16 abstract images with one of two response categories. Each trial had a 50% chance of being eligible for informative feedback. If ineligible, the response was followed by the feedback message “Unknown”. In the positive feedback condition, the feedback message “Correct” was displayed if the trial was eligible for feedback and the response was correct; otherwise the message “Unknown” was shown. Similarly, the message “Incorrect” was presented on eligible trials in the negative feedback condition when the answer was incorrect. In this manner, we separated positive and negative feedback-based learning. Participants were tested in two sessions in a double blind study. In one session participants ingested 1.25 mg of Bromocriptine (BR), a DA agonist; in the other session, they were given a placebo (PLAC).
On placebo, performance was more accurate in the positive condition (90%) than in the negative condition (83%). Overall, there was a Drug x Reinforcement Type interaction: BR resulted in a drop in accuracy for the positive condition and an increase in accuracy for negative condition. The reduction in performance from BR during positive reinforcement was similar for all alleles of COMT. In contrast, the benefit from BR during negative reinforcement was restricted to those individuals with higher levels of intrinsic DA (Val/Met or Met/MET alleles). For DRD2, the interaction of BR and reinforcement type was most pronounced in individuals with lower levels of intrinsic DA (A/A or A/G). These results suggest that individuals with higher DA levels in the frontal lobe may benefit in learning from negative feedback when DA signaling is increased, while individuals with lower striatal levels of DA may benefit in learning from both types of feedback with increased DA signaling.

The role of dopamine in reward is a topic of debate. For example, some have argued that phasic dopamine signaling provides a prediction-error signal necessary for stimulus-reward learning, whereas others have hypothesized that dopamine is not necessary for learning per se, but for attributing incentive motivational value (“incentive salience”) to reward cues. These psychological processes are difficult to tease apart, because they tend to change together. To disentangle them we took advantage of natural individual variation in the extent to which reward cues are attributed with incentive salience, and asked whether dopamine (specifically in the core of the nucleus accumbens) is necessary for the expression of two forms of Pavlovian conditioned approach behavior - one in which the cue acquires powerful motivational properties (sign-tracking) and another closely related one in which it does not (goal-tracking). After acquisition of these conditioned responses (CRs), intra-accumbens injection of the dopamine receptor antagonist flupenthixol markedly impaired the expression of a sign-tracking CR, but not a goal-tracking CR. Furthermore, dopamine antagonism did not produce a gradual extinction-like decline in behavior, but maximally impaired expression of a sign-tracking CR on the very first trial, indicating the effect was not due to new learning (i.e., it occurred in the absence of new prediction-error computations). The data support the view that dopamine in the accumbens core is not necessary for learning stimulus-reward associations, but in attributing incentive salience to reward cues, transforming predictive CSs into incentive stimuli with powerful motivational properties.

It was previously reported that adenosine-2A (A2A) receptors interact with dopamine-2 (D2) receptors on a molecular level. The aim of the current study was to investigate the functional output of this interaction. In vivo microdialysis was used to assess the effects of an antagonist of A 2A receptors, ZM 241385, and an antagonist of D2 receptors haloperidol, either alone or in combination, on brain catecholamine levels. It was found that ZM 241385 did not alter catecholamine levels by its own, but potentiated haloperidol-induced dopamine and norepinephrine release in the nucleus accumbens and prefrontal cortex, respectively. In vivo electrophysiology was used to assess the effect of an agonist (CGS 216820) and an antagonist (ZM 241385) of A 2A receptors on the excitability of dopamine and norepinephrine neurons. It was found that CGS 216820 dose-dependently inhibited dopamine and norepinephrine neurons and ZM 241385 reversed this inhibition. In conclusion, those A 2A receptors modulate brain catecholamine transmission, and this modulation is mediated, at least in part, via the regulation of excitability of norepinephrine and dopamine neurons. The ability of antagonists of A2A receptors to potentiate the effect of haloperidol on brain norepinephrine and dopamine levels may enhance its clinical efficacy as an antipsychotic drug.

Different data show that circulating lymphocytes possess functional serotonin and dopamine transporters (SERT and DAT, respectively). This papers aims to review most of the available literature on this topic, while highlighting the possible role of SERT and DAT, as well as that of their substrates including antidepressants on the immune system.

The current essay introduces and describes the mechanisms of action and discusses the plethora of functional neuroimaging (fNI) modalities applicable while also detailing the theoretical framework behind psychosis. The essay also comments on a range of anti-psychotic agents and relates the fNI methods as invaluable instruments of investigation for examination of anti-psychotic agents. The author concludes that fNI techniques have informed the academic community, aiding the clinical environment and highlights possible directions of future research.

Interpreting others' actions is essential for understanding the intentions and goals in social interactions. Activity in the motor cortex is evoked when we see another person performing actions, which can also be influenced by the intentions and context of the observed action. No study has directly explored the influence of reward and punishment on motor cortex activity when observing others' actions, which is likely to have substantial relevance in different social contexts. In this experiment, EEG was recorded while participants watched movie clips of a person performing actions that led to a monetary reward, loss or no change for the observer. Using the EEG mu rhythm as an index of motor resonance, our results demonstrate that observation of rewarding actions produce significantly greater motor cortex activity than punishing or neutral actions, with punishing actions producing greater activity than neutral ones. In addition, the dynamic change in the mu rhythm over sensorimotor cortex is modulated by reward and punishment, with punishing actions producing a prolonged suppression. These findings demonstrate that the associated reward value of an observed action may be crucial in determining the strength of the representation of the action in the observer's brain. Consequently, reward and punishment is likely to drive observational learning through changes in the action observation network, and may also influence how we interpret, understand, engage in and empathize with others' actions in social interaction.

There is little evidence to date to indicate if mesoac-cumbens dopamine function at the neurochemical level is altered during early abstinence from chronic i.v. nicotine self-administration. Thus, a quantitative microdialysis (no-net-flux) approach was used to measure basal extracellular concentrations and extraction fractions of dopamine in the nucleus ac-cumbens (ACB) of rats that self-administered nicotine i.v. for 25 days, as well as in rats serving as yoked comparison groups (yoked nicotine and yoked saline). After 24-48 h of the final self-administration session, there was a significant reduction in basal extracellular dopamine levels in the ACB of the self-administration group compared with the yoked saline group (1.35؎0.15 nM versus 3.70؎0.28 nM). The basal extracellular dopamine levels in the yoked nicotine group (1.46؎0.20 nM) were not significantly different compared with the nicotine self-administration group. The in vivo extraction fraction of dopa-mine, an indirect measure of dopamine uptake, was significantly increased in the nicotine self-administration (86%) and yoked nicotine (91%) groups compared with the yoked saline group (77%). In addition, a marked reduction in the elevation of extracellular dopamine levels in the ACB occurred after a nicotine challenge as measured by conventional microdialysis in the self-administration (112% of basal) and yoked nicotine (121% of basal) groups as compared with a yoked saline (154% of basal) group. The reduced basal ACB dopamine levels in the nicotine groups during early abstinence appears to be due to increased clearance, suggesting increased dopamine uptake is occurring as a result of the chronic nicotine treatment. The reduced elevation of extracellular dopamine levels in the ACB upon nicotine challenge suggests a functional desensitization or downregulation phenomenon involving acetylcholine receptors (nicotinic nAChRs). Overall, these results provide clear evidence for a neuroadaptive change that alters dopamine transmission in the ACB during abstinence from chronic i.v. nicotine exposure.

Background: The antidepressant effect of physical exercise has been reported in several clinical and animal studies. Since serotonin (5-HT), norepinephrine and dopamine play a central role in depression, it is possible that the beneficial effects of physical exercise are mediated via monoamine pathways. This study investigates the effects of voluntary wheel running (VWR) on the excitability of monoamine neurons.
Material and methods: Male Sprague-Dawley rats were used in the study. Voluntary wheel running (VWR) rats were housed in individual cages with free access to a running wheel, while control animals were housed in standard laboratory cages. After three weeks, the rats were anesthetized and in vivo electrophysiological recordings
were taken from dorsal raphe nucleus 5-HT neurons, locus coeruleus norepinephrine neurons and ventral tegmental dopamine neurons.
Results: VWR stimulated activity in 5-HT, but not in norepinephrine or dopamine neurons. Subsequently, acute administration of the selective serotonin reuptake inhibitor (SSRI) escitalopram in control rats led to complete suppression of 5-HT neurons; this suppression was reversed by subsequent administration of selective antagonist of 5-HT1A receptors, WAY100135. Escitalopram induced only partial inhibition of 5-HT neurons in the VWR rats while WAY100135 increased the firing
activity of 5-HT neurons above the baseline value.
Conclusions: The beneficial effect of physical exercise on mood is mediated, at least in part, via activation of 5-HT neurons. Physical exercise can potentiate the response to SSRIs by increasing the basal firing activity and by diminishing SSRI induced inhibition of 5-HT neurons.

To assess the relationship between cognitive function, a proposed schizophrenia endophenotype, and two genetic polymorphisms related to dopamine function, catechol-O-methyl transferase (COMT) Val158Met and dopamine receptor 3 (DRD3) Ser9Gly. Fifty-eight outpatients with schizophrenia/schizoaffective disorder and 88 healthy controls underwent neurocognitive testing and genotyping. Analyses of covariance (ANCOVAs) using age, sex, and years of education as covariates compared cognitive performance for the proposed genotypes in patients and controls. ANCOVAs also tested for the epistatic effect of COMT and DRD3 genotype combinations on cognitive performance. For executive functioning, COMT Val/Val patients performed in a similar range as controls (30.70-33.26 vs. 35.53-35.67), but as COMT Met allele frequency increased, executive functioning worsened. COMT Met/Met patients carrying the DRD3 Ser/Ser genotype performed poorest (16.184 vs. 27.388-31.824). Scores of carriers of this COMT/DR...

While most patients with depression respond to combinations of pharmacotherapy, psychotherapy, and electroconvulsive therapy (ECT), there are patients requiring other treatments. Deep brain stimulation (DBS) allows modulation of brain regions that are dysfunctional in depression. Since anhedonia is a feature of depression and there is evidence of dysfunction of the reward system, DBS to the nucleus accumbens (NAcc) might be promising. Ten patients suffering from very resistant forms of depression (treatment-resistant depression [TRD]), not responding to pharmacotherapy, psychotherapy, or ECT, were implanted with bilateral DBS electrodes in the NAcc. The mean (+/-SD) length of the current episode was 10.8 (+/-7.5) years; the number of past treatment courses was 20.8 (+/-8.4); and the mean Hamilton Depression Rating Scale (HDRS) was 32.5 (+/-5.3). Twelve months following initiation of DBS treatment, five patients reached 50% reduction of the HDRS (responders, HDRS = 15.4 [+/-2.8]). The number of hedonic activities increased significantly. Interestingly, ratings of anxiety (Hamilton Anxiety Scale) were reduced in the whole group but more pronounced in the responders. The [18F]-2-fluoro-2-deoxy-D-glucose positron emission tomography data revealed that NAcc-DBS decreased metabolism in the subgenual cingulate and in prefrontal regions including orbital prefrontal cortex. A volume of interest analysis comparing responders and nonresponders identified metabolic decreases in the amygdala. We demonstrate antidepressant and antianhedonic effects of DBS to NAcc in patients suffering from TRD. In contrast to other DBS depression studies, there was also an antianxiety effect. These effects are correlated with localized metabolic changes.

Postmortem brain specimens from nine chronic schizophrenic patients and nine control were assayed for activity of dopamine beta-hydroxylase, the enzyme responsible for the conversion of dopamine to norepinephrine. Unlike the results of previous reports, there was no statistically significant difference in enzyme activity between the patient and control groups. There were, however, significant negative correlations between dopamine beta-hydroxylase activity and the tim spent in the morgue before autopsy, and between enzyme activity of schizophrenics and dosage of chlorpromazine or its equivalent.

Long-term survival of mesencephalic and
striatal cells from mouse embryos in dissociated primary cultures
is described. Catecholaminergic neurons in mesencephalic
cultures were identified histochemically and by measuring
[3Hldopamine uptake and synthesis from [3Hltyrosine. According
to experiments using specific inhibitors of catecholamine
uptake, at least two-thirds of the catecholaminergic
neurons are dopaminergic. These neurons differentiated
whether or not striatal target cells were present, but striatal cells
stimulated the development of the dopaminergic neurons.
I3Hlopamine uptake was increased by at least 2-fold regardless
of the age of the cocultures (4-15 days). Enhanced [3H]dopamine
synthesis was also observed (at least 2-fold) at later times (12-15
days).