The anxiolytic neurosteroid allopregnanolone (3alpha-hydroxy-5alpha-pregnan-20-one or 3alpha,5alp... more The anxiolytic neurosteroid allopregnanolone (3alpha-hydroxy-5alpha-pregnan-20-one or 3alpha,5alpha-THP) has been proposed to play a developmental role in emergent neural regulation of affective behavior. This experiment examined whether allopregnanolone administered during the last week of gestation in rats would alter neonatal and adult offspring behaviors in the selectively-bred High vocalizing line, who have low levels of allopregnanolone and high levels of anxious/depressive behaviors. Dams were injected twice a day with the neurosteroid or vehicle, or handled as controls, and were tested on the elevated plus maze just before parturition. Maternal behavior was assessed throughout the first week of life, and affective behavior in the offspring was tested at one week of age (ultrasonic vocalizations test) and as adults (plus maze and forced swim tests). Offspring prenatally exposed to allopregnanolone were less anxious as neonates and less depressed as adults compared to both control groups. Only male adult offspring, however, revealed less anxious behavior on the plus maze. Neither the dams' anxiety behavior measured in late gestation nor their postnatal maternal behavior was altered compared to controls, suggesting a direct, long-lasting effect of gestational allopregnanolone on the developing fetal brain independent of mediating maternal factors. These results are discussed in light of new evidence about the developmental role of the GABA-A receptor prenatally.
Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism, Jan 7, 2015
Glucose metabolism has been associated with magnitude of blood oxygen level-dependent (BOLD) sign... more Glucose metabolism has been associated with magnitude of blood oxygen level-dependent (BOLD) signal and connectivity across subjects within the default mode and dorsal attention networks. Similar correlations within subjects across the entire brain remain unexplored. [(18)F]-fluorodeoxyglucose positron emission tomography ([(18)F]-FDG PET), [(11)C]-flumazenil PET, and resting-state functional magnetic resonance imaging (fMRI) scans were acquired in eight healthy individuals and nine with temporal lobe epilepsy (TLE). Regional metabolic rate of glucose (rMRGlu) was correlated with amplitude of low frequency fluctuations (ALFFs) in the fMRI signal, global fMRI connectivity (GC), regional homogeneity (ReHo), and gamma-aminobutyric acid A-binding potential (GABAA BPND) across the brain. Partial correlations for ALFFs, GC, and ReHo with GABAA BPND were calculated, controlling for rMRGlu. In healthy subjects, significant positive correlations were observed across the brain between rMRGlu ...
Communal nesting (CN) is a mouse model of early social enrichment during pregnancy and lactation.... more Communal nesting (CN) is a mouse model of early social enrichment during pregnancy and lactation. In this study, a rat model of CN was developed to determine if CN exerts an epigenetic effect in rats selectively bred for an infantile affective trait (high and low rates of ultrasonic distress calls). High and Low offspring from CN groups were compared to standard reared (SN) offspring on five measures of social and affective behavior at three critical ages. A differential effect of the CN paradigm on High and Low lines was seen in measures of anxiety and arousal, but not in measures of depression or social behavior. Neonatal CN subjects emitted fewer distress calls than SN subjects when separated from their dams, and the High line subjects were more affected by the CN procedure. As juveniles, CN subjects showed increased social behaviors in tests of juvenile parenting and play compared to SN subjects. In adulthood, CN differentially increased the activity of Low line subjects. All CN subjects displayed less anxiety behavior in an open field compared to SN subjects; High line subjects were more anxious than Lows. CN reduced immobility and increased attempts to escape on the Porsolt forced swim task relative to SN subjects. These results extend the usefulness of this early enrichment paradigm from mice to rats, and found some rodent species differences in outcomes dependent on the behavioral test. They also emphasize the importance of social contact during pregnancy and lactation on offspring's optimal development across behaviors and ages.
The anxiolytic neurosteroid allopregnanolone (3alpha-hydroxy-5alpha-pregnan-20-one or 3alpha,5alp... more The anxiolytic neurosteroid allopregnanolone (3alpha-hydroxy-5alpha-pregnan-20-one or 3alpha,5alpha-THP) has been proposed to play a developmental role in emergent neural regulation of affective behavior. This experiment examined whether allopregnanolone administered during the last week of gestation in rats would alter neonatal and adult offspring behaviors in the selectively-bred High vocalizing line, who have low levels of allopregnanolone and high levels of anxious/depressive behaviors. Dams were injected twice a day with the neurosteroid or vehicle, or handled as controls, and were tested on the elevated plus maze just before parturition. Maternal behavior was assessed throughout the first week of life, and affective behavior in the offspring was tested at one week of age (ultrasonic vocalizations test) and as adults (plus maze and forced swim tests). Offspring prenatally exposed to allopregnanolone were less anxious as neonates and less depressed as adults compared to both control groups. Only male adult offspring, however, revealed less anxious behavior on the plus maze. Neither the dams' anxiety behavior measured in late gestation nor their postnatal maternal behavior was altered compared to controls, suggesting a direct, long-lasting effect of gestational allopregnanolone on the developing fetal brain independent of mediating maternal factors. These results are discussed in light of new evidence about the developmental role of the GABA-A receptor prenatally.
The anxiolytic neurosteroid allopregnanolone (3alpha-hydroxy-5alpha-pregnan-20-one or 3alpha,5alp... more The anxiolytic neurosteroid allopregnanolone (3alpha-hydroxy-5alpha-pregnan-20-one or 3alpha,5alpha-THP) has been proposed to play a developmental role in emergent neural regulation of affective behavior. This experiment examined whether allopregnanolone administered during the last week of gestation in rats would alter neonatal and adult offspring behaviors in the selectively-bred High vocalizing line, who have low levels of allopregnanolone and high levels of anxious/depressive behaviors. Dams were injected twice a day with the neurosteroid or vehicle, or handled as controls, and were tested on the elevated plus maze just before parturition. Maternal behavior was assessed throughout the first week of life, and affective behavior in the offspring was tested at one week of age (ultrasonic vocalizations test) and as adults (plus maze and forced swim tests). Offspring prenatally exposed to allopregnanolone were less anxious as neonates and less depressed as adults compared to both control groups. Only male adult offspring, however, revealed less anxious behavior on the plus maze. Neither the dams' anxiety behavior measured in late gestation nor their postnatal maternal behavior was altered compared to controls, suggesting a direct, long-lasting effect of gestational allopregnanolone on the developing fetal brain independent of mediating maternal factors. These results are discussed in light of new evidence about the developmental role of the GABA-A receptor prenatally.
Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism, Jan 7, 2015
Glucose metabolism has been associated with magnitude of blood oxygen level-dependent (BOLD) sign... more Glucose metabolism has been associated with magnitude of blood oxygen level-dependent (BOLD) signal and connectivity across subjects within the default mode and dorsal attention networks. Similar correlations within subjects across the entire brain remain unexplored. [(18)F]-fluorodeoxyglucose positron emission tomography ([(18)F]-FDG PET), [(11)C]-flumazenil PET, and resting-state functional magnetic resonance imaging (fMRI) scans were acquired in eight healthy individuals and nine with temporal lobe epilepsy (TLE). Regional metabolic rate of glucose (rMRGlu) was correlated with amplitude of low frequency fluctuations (ALFFs) in the fMRI signal, global fMRI connectivity (GC), regional homogeneity (ReHo), and gamma-aminobutyric acid A-binding potential (GABAA BPND) across the brain. Partial correlations for ALFFs, GC, and ReHo with GABAA BPND were calculated, controlling for rMRGlu. In healthy subjects, significant positive correlations were observed across the brain between rMRGlu ...
Communal nesting (CN) is a mouse model of early social enrichment during pregnancy and lactation.... more Communal nesting (CN) is a mouse model of early social enrichment during pregnancy and lactation. In this study, a rat model of CN was developed to determine if CN exerts an epigenetic effect in rats selectively bred for an infantile affective trait (high and low rates of ultrasonic distress calls). High and Low offspring from CN groups were compared to standard reared (SN) offspring on five measures of social and affective behavior at three critical ages. A differential effect of the CN paradigm on High and Low lines was seen in measures of anxiety and arousal, but not in measures of depression or social behavior. Neonatal CN subjects emitted fewer distress calls than SN subjects when separated from their dams, and the High line subjects were more affected by the CN procedure. As juveniles, CN subjects showed increased social behaviors in tests of juvenile parenting and play compared to SN subjects. In adulthood, CN differentially increased the activity of Low line subjects. All CN subjects displayed less anxiety behavior in an open field compared to SN subjects; High line subjects were more anxious than Lows. CN reduced immobility and increased attempts to escape on the Porsolt forced swim task relative to SN subjects. These results extend the usefulness of this early enrichment paradigm from mice to rats, and found some rodent species differences in outcomes dependent on the behavioral test. They also emphasize the importance of social contact during pregnancy and lactation on offspring's optimal development across behaviors and ages.
The anxiolytic neurosteroid allopregnanolone (3alpha-hydroxy-5alpha-pregnan-20-one or 3alpha,5alp... more The anxiolytic neurosteroid allopregnanolone (3alpha-hydroxy-5alpha-pregnan-20-one or 3alpha,5alpha-THP) has been proposed to play a developmental role in emergent neural regulation of affective behavior. This experiment examined whether allopregnanolone administered during the last week of gestation in rats would alter neonatal and adult offspring behaviors in the selectively-bred High vocalizing line, who have low levels of allopregnanolone and high levels of anxious/depressive behaviors. Dams were injected twice a day with the neurosteroid or vehicle, or handled as controls, and were tested on the elevated plus maze just before parturition. Maternal behavior was assessed throughout the first week of life, and affective behavior in the offspring was tested at one week of age (ultrasonic vocalizations test) and as adults (plus maze and forced swim tests). Offspring prenatally exposed to allopregnanolone were less anxious as neonates and less depressed as adults compared to both control groups. Only male adult offspring, however, revealed less anxious behavior on the plus maze. Neither the dams' anxiety behavior measured in late gestation nor their postnatal maternal behavior was altered compared to controls, suggesting a direct, long-lasting effect of gestational allopregnanolone on the developing fetal brain independent of mediating maternal factors. These results are discussed in light of new evidence about the developmental role of the GABA-A receptor prenatally.
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