Mineralocorticoid and glucocorticoid receptor-mediated effects on serotonergic transmission in health and disease.
Corticosterone is released in large amounts from the rat and mouse adrenal gland after stress. The hormone enters the brain and binds to intracellular receptors. Previously, we found that rises in the corticosterone level, as after acute stressors, enhance the response of hippocampal CA1 neurons to serotonin (5-HT), which hyperpolarizes the membrane via the 5-HT1A receptor. Recently, we examined how 5-HT responses are affected by more persistent changes in circulating hormone levels. In chronically stressed rats, we observed that 5-HT responses with both basal and high corticosterone levels are attenuated compared to those in the controls; 5-HT1A receptor expression was not altered. Similarly, in long-attack latency mice, which are characterized by a hyperresponsive hypothalamus-pituitary-adrenal axis, 5-HT responses were diminished, accompanied by reduced receptor expression. Finally, rats that for 24 h were deprived of their mother at postnatal day 3 exhibited attenuated 5-HT responses when tested at 3 months of age, in the absence of changes in the 5-HT1A receptor expression. We conclude that prolonged exposure to elevated corticosterone levels attenuates 5-HT responses in the hippocampus through an unresolved mechanism. This may be relevant to the observation that hypercortisolism in humans is a risk factor for the precipitation of major depression in genetically predisposed individuals.
Joëls
Marian
M
Swammerdam Institutes for Life Sciences, Section Neurobiology, University of Amsterdam, Kruislaan 320, 1098 SM, Amsterdam, the Netherlands. Joels@science.uva.nl
Van Riel
Els
E
D000374:Aggression; D000818:Animals; D004247:DNA / Q000378:metabolism; D004194:Disease; D004305:Dose-Response Relationship, Drug; D005260:Female; D006262:Health; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism; D008297:Male; D008426:Maternal Deprivation; D009474:Neurons / Q000378:metabolism; D051381:Rats; D011965:Receptors, Glucocorticoid / Q000502:physiology*; D018161:Receptors, Mineralocorticoid / Q000502:physiology*; D012701:Serotonin / Q000502:physiology*; D013315:Stress, Psychological / Q000503:physiopathology; D009435:Synaptic Transmission / Q000502:physiology*; D015430:Weight Gain / Q000187:drug effects
D011965:Receptors, Glucocorticoid; D018161:Receptors, Mineralocorticoid; D012701:Serotonin; D004247:DNA