Receptors

The concept of specific receptors that bind drugs or transmitter substances onto the cell, thereby either initiating biological effects or inhibiting cellular functions, is today a cornerstone of pharmacological research and pharmaceutical development. Yet, while the basic ideas of this concept were first explicitly formulated in 1905 by the Cambridge physiologist John Newport Langley (1852–1925), drug receptors remained hypothetical entities at least until the end of the 1960s. Without doubt, the development of receptor-subtype specific pharmaceuticals—especially the beta-adrenergic receptor antagonist propranolol (introduced in 1965)—promoted the acceptance of the receptor concept in pharmacology. It was only in the 1970s, however, that receptors began to be isolated as specific proteins of the cell membrane and that their composition and conformation began to be explored. During the last twenty years the modern techniques of molecular biology have helped to determine the genetic ...

Abstract: ADHD is a polygenic disorder due to the additive effect of genes affecting dopamine, norepinephrine, serotonin, GABA, and other neurotransmitters. Some of the specific loci involved are dopamine genes—DRD2, DRD4, DRD5, and the dopamine transporter; norepinephrine (NE) and epinephrine (EPI) genes—dopamine b-hydroxylase, ADRA2A, ADRA2C, PNMT, norepinephrine transporter, MAOA, COMT; serotonin genes—TDO2, HTR1A, HTR1DA, serotonin transporter; GABA genes—GABRB3; androgen receptor and other genes. This model is consistent with all of the present knowledge about ADHD including (a) the increased frequency of ADHD in the relatives of ADHD probands, (b) the presence of a wide spectrum of comorbid behaviors (depression, anxiety, learning, conduct, oppositional-defiant, conduct and substance abuse disorders) in ADHD probands and their relatives on both parental sides, (c) the close relationship to Tourette syndrome (TS), (d) the failure to find the genes for TS using linkage analysis, (e) the brain imaging studies showing hypometabolism of the frontal lobes, (f) the relationship between dopamine D2 receptor density and regional blood flow, (g) the correlation between tics and dopamine D2 receptor density in TS, (h) the motor hyperactivity of dopamine transporter and dopamine D3 receptor gene knockout mice, (i) the LeMoal and Shaywitz dopamine deficiency animal models of ADHD, (j) the NE models of ADHD, (k) the failure to explain ADHD on the basis of any single neurotransmitter defect, (l) the response of ADHD to dopamine and a2-adrenergic agonists, (m) the small percentage of the variance of specific behaviors accounted for by each gene, and numerous other aspects of ADHD. The implications of the polygenic model for the understanding, diagnosis and treatment of ADHD and TS, as well as other psychiatric disorders, are reviewed.

This target article suggests a new interpretation of efferent influences on sensory receptor activity and the role of the senses in forming knowledge. Experimental data and a thought experiment about a hypothetical motor-only organism suggest that the senses are not transmitters of environmental information; rather, they create a direct connection between the organism and the environment that makes possible a dynamic organism-environment system. In this system efferent influences on receptor activity are especially critical, because with their help the receptors can be adjusted in relation to the parts of the environment that are most important in achieving behavioral results. Perception joins new parts of the environment to the organism-environment system; thus knowledge is formed by perception through a reorganization (a widening and differentiation) of the organism-environment system rather than through the transmission of information from the environment. With the help of efferent effects on receptors, each organism creates its own particular world. These considerations have implications for experimental work in the neurophysiology and psychology of perception as well as for the philosophy of knowledge formation.

Chromium (Cr) (III), an essential microelement of living organisms, was reported to exhibit potential antidepressant properties in preclinical and clinical studies. The aim of the present study was to examine the effect of CrCl(3) ip administration in the forced swim test (FST) in mice and the involvement of glutamatergic and serotonergic receptors in the antidepressant-like activity of chromium. CrCl(3) in a dose of 12 mg/kg, but not in doses of 6 or 32 mg/kg, reduced the immobility time in the FST. The locomotor activity was reduced by CrCl(3) in a dose of 32 mg/kg. Moreover, the reduction of the immobility time induced by the active dose (12 mg/kg) of CrCl(3) was completely abolished by NBQX (10 mg/kg; an antagonist of the AMPA receptor) pretreatment and partially inhibited by ritanserin (4 mg/kg; an antagonist of 5-HT(2A/C) receptor), WAY 1006335 (0.1 mg/kg; an antagonist of 5-HT(1A) receptor) and N-methyl-D-aspartate (75 mg/kg; agonist of NMDA receptor) administration. The pres...