Acute rise in corticosterone facilitates 5-HT(1A) receptor-mediated behavioural responses.
Corticosterone influences 5-HT1A receptor-mediated responses in the rat hippocampus in vitro: activation of the high affinity mineralocorticoid receptor suppresses 5-HT1A receptor-mediated hyperpolarization, while subsequent activation of lower affinity glucocorticoid receptors enhances the effect of 5-HT. We have tested whether a similar effect of corticosterone exists in vivo. In intact rats, a systemic injection of the specific 5-HT1A receptor agonist, 8-OH-DPAT (8-hydroxy-2-(di-n-propylamino)tetralin), led to increased locomotion and to a less persistent search strategy in the free swim trial of the Morris water maze test. Adrenalectomized rats with a corticosterone-pellet implanted as replacement received an injection of vehicle (predominant mineralocorticoid receptor occupation) or a high dose of corticosterone (both corticosteroid receptor types occupied) 1 h before injection of 8-OH-DPAT. The effect on search strategy, but not on locomotor activity, was less in animals with low corticosterone levels. The results suggest that hippocampal 5-HT1A receptor-mediated responses in vivo are attenuated during predominant activation of the mineralocorticoid receptor and increased after additional transient activation of the glucocorticoid receptor.
Division of Medical Pharmacology, Leiden/Amsterdam Center for Drug Research, Netherlands.
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Meijer
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Kortekaas
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Oitzl
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de Kloet
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000008:administration & dosage / Q000494:pharmacology*; D000315:Adrenalectomy; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D003345:Corticosterone / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004343:Drug Implants; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D009043:Motor Activity / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D011965:Receptors, Glucocorticoid / Q000187:drug effects / Q000378:metabolism; D018161:Receptors, Mineralocorticoid / Q000187:drug effects / Q000378:metabolism; D011985:Receptors, Serotonin / Q000187:drug effects* / Q000378:metabolism; D044263:Receptors, Serotonin, 5-HT1; D017366:Serotonin Receptor Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D013037:Spatial Behavior / Q000187:drug effects
D004343:Drug Implants; D011965:Receptors, Glucocorticoid; D018161:Receptors, Mineralocorticoid; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D017366:Serotonin Receptor Agonists; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D003345:Corticosterone