Pharmacological modulation of glucocorticoid and mineralocorticoid receptors in the rat central nervous system.
This review examines neurochemical mechanisms of the corticosteroid receptor regulation in the central nervous system. Glucocorticoid (GRs) and mineralocorticoid (MRs) receptors are localized in discrete brain regions, especially in the limbic system, and exert inhibitory control over the hypothalamic-pituitary-adrenal (HPA) axis; moreover, they are found to affect the responsiveness of neurotransmitters. The GR and MR levels and biosynthesis appear to be under a serotoninergic and, to a lesser extent, a noradrenergic, cholinergic and dopaminergic influence. Of the neuropeptides studied, vasopressin and ACTH regulate the corticosteroid receptor density. The above data strongly suggest that GR and MR may be affected by some psychotropic drugs which are known to cause alterations in classic neurotransmitter systems. In this respect, adaptive changes in GR and MR parameters, evoked by drugs which are commonly administered for a long time, e.g. antidepressants or drugs of abuse, seem to be of particular interest. Long-term treatment with tricyclic antidepressants such as imipramine, desipramine, amitriptyline and maprotiline elevates the density and/or biosynthesis of GR and/or MR. Similar effects are observed after chronic lithium or repeated electroconvulsive shock (ECS), which suggests that alterations in corticosteroid receptors may be involved in the mechanism of their antidepressant action. On the other hand, chronic administration of drugs of abuse, such as amphetamines or morphine, down-regulates GR which may impair the feedback control mechanism of the HPA activity.
Budziszewska
B
B
Department of Endocrinology, Polish Academy of Sciences, Kraków.
Lasoń
W
W
D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000008:administration & dosage / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002490:Central Nervous System / Q000187:drug effects* / Q000378:metabolism; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000187:drug effects; D006801:Humans; D013287:Illicit Drugs / Q000494:pharmacology* / Q000633:toxicity; D051381:Rats; D011965:Receptors, Glucocorticoid / Q000187:drug effects* / Q000378:metabolism; D018161:Receptors, Mineralocorticoid / Q000187:drug effects* / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects
D000929:Antidepressive Agents, Tricyclic; D013287:Illicit Drugs; D011965:Receptors, Glucocorticoid; D018161:Receptors, Mineralocorticoid