Neuroscience
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Early exposure to adverse experiences may lead to specific changes in hippocampal glucocorticoid function resulting in abnormalities within the hypothalamic-adrenal axis. Given interactions between the neuroendocrine and central serotonergic systems, we hypothesized that exposure to early trauma would lead to abnormal hypothalamic-adrenal axis activity that would be normalized by pretreatment with a selective serotonin re-uptake inhibitor. Hypothalamic-adrenal axis function was assessed by determining basal corticosterone levels and hippocampal glucocorticoid receptor immunoreactivity. ⋯ Animals exposed to early life trauma showed an increase in basal corticosterone levels, and a significant decrease in the ratio of glucocorticoid receptor positive cells to total cells in the hilus, granule cell layer and the dentate gyrus. Both the increase in basal corticosterone and decrease in glucocorticoid receptor immunoreactivity were reversed by escitalopram pretreatment. These data confirm alterations in hypothalamic-adrenalaxis function that may stem from decreases in glucocorticoid receptor levels, in response to early adverse experiences, and demonstrate that these alterations are reversed by serotonin re-uptake inhibitor pretreatment.
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The suprachiasmatic nucleus of the hypothalamus is the master circadian clock in mammals. Phase shifts in circadian locomotor activity occur when an animal is exposed to light during the subjective night. An endogenous ligand of opioid receptor like 1, nociceptin is reported to inhibit light-induced phase shifts in locomotor activity rhythm. ⋯ Compound B (30 mg/kg, i.p.) significantly potentiated the light-induced phase delay. Nociceptin induced a neuronal firing phase advance (in vitro) and locomotor activity rhythms (in vivo) in the daytime and this effect was blocked by Compound B. These results suggest that opioid receptor like 1 receptors have an inhibitory effect at night, and a facilitative effect in the day, on phase changes.
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Behavioral evidence supports a role for peripheral glutamate receptors in normal nociceptive transmission. In this study, we examined the release of the excitatory amino acids, glutamate and aspartate, in the s.c. perfusate of the rat hind instep by in vivo microdialysis. Antidromic stimulation of the sciatic nerve and noxious stimuli in the form of heat stimulation and local application of capsaicin cream (1%) to the instep caused an increase in excitatory amino acid release. ⋯ Both systemic (10 mg/kg, i.v.) and local injections (10(-5) M in the perfusate) of morphine inhibited the increase in excitatory amino acid release evoked by local application of capsaicin cream to the instep. This inhibitory effect of morphine was antagonized by naloxone either given systemically (5 mg/kg, i.v.) or locally (10(-5) M). These results suggest that excitatory amino acids are released from small diameter afferent fibers by heat stimulation in the periphery or local application of capsaicin cream, and that activation of opioid receptors, present on the peripheral endings of small-diameter afferent fibers, can regulate noxious stimulus-induced excitatory amino acid release.
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Progestins mediate the onset and duration of lordosis, the mating posture of female rodents, through actions in the hypothalamus and ventral tegmental area. In the hypothalamus, progesterone has traditional, "genomic" actions via intracellular progestin receptors. ⋯ Data are reviewed that support the notion that: 1) effects of 3alpha-hydroxy-5alpha-pregnan-20-one in the midbrain ventral tegmental area facilitate lordosis and other reproductively-relevant behaviors. 2) 3alpha-Hydroxy-5alpha-pregnan-20-one, formed in the ventral tegmental area from metabolism of progestins, produced peripherally by endocrine glands, or centrally from biosynthesis in glial cells mediates socio-sexual behaviors. 3) 3alpha-Hydroxy-5alpha-pregnan-20-one's actions at GABA(A)/benzodiazepine receptors, NMDA type glutamate receptors, and dopamine receptors in the ventral tegmental area are important for lordosis; however, effects at these substrates on socio-sexual behaviors have not been elucidated. Given 3alpha-hydroxy-5alpha-pregnan-20-one's involvement in stress responses, its putative role as a homeostatic regulator and in the pathophysiology and treatment of neuropsychiatric disorders is discussed.
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Previous studies have demonstrated that macromolecular synthesis in the brain is modulated in association with the occurrence of sleep and wakefulness. Similarly, the spectral composition of electroencephalographic activity that occurs during sleep is dependent on the duration of prior wakefulness. Since this homeostatic relationship between wake and sleep is highly conserved across mammalian species, genes that are truly involved in the electroencephalographic response to sleep deprivation might be expected to be conserved across mammalian species. ⋯ Using Affymetrix Neurobiology U34 GeneChips , we also screened the rat cerebral cortex, basal forebrain, and hypothalamus for other genes whose expression may be modulated by sleep deprivation or recovery sleep. We find that the response of the basal forebrain to sleep deprivation is more similar to that of the cerebral cortex than to the hypothalamus. Together, these results suggest that sleep-dependent changes in gene expression in the cerebral cortex are similar across rodent species and therefore may underlie sleep history-dependent changes in sleep electroencephalographic activity.