Serotonin regulates type II corticosteroid receptor binding in hippocampal cell cultures.
Previous work from our laboratory has shown that early postnatal handling of rat pups permanently increases hippocampal type II, but not type I, corticosteroid receptor binding. Handling also increases hippocampal 5-HT turnover, and the effect of handling on type II corticosteroid receptor binding is blocked by concurrent administration of the 5-HT2 receptor antagonist ketanserin. In view of these findings, the present studies examined the effects of 5-HT on type I ([3H]corticosterone) and type II ([3H]RU 28362) corticosteroid receptor binding in dispersed hippocampal cell cultures derived from animals killed at E19-20 in order to verify that 5-HT can act directly on hippocampal cells to alter corticosteroid receptor binding. Both type I and type II receptors were measurable in cultured hippocampal cells and the apparent affinity (Kd) for [3H]corticosterone (0.4 +/- 0.1 nM) and [3H]RU 28362 (0.8 +/- 0.1 nM) was similar to that from studies with intact animals. 5-HT increased type II, but not type I, corticosteroid receptor binding capacity in a dose-related manner, with the maximal effect (+188%) observed at 10 nM 5-HT and no change in the affinity of the receptor for [3H]RU 28362. The effect of 10 nM 5-HT on [3H]RU 28362 binding required a minimum of 4 d exposure and persisted for at least 7 d following the removal of 5-HT. The effect of 10 nM 5-HT on [3H]RU 28362 binding was completely blocked by the 5-HT2 receptor antagonists ketanserin and mianserin. There were no effects of the 5-HT1a antagonist, BMY 7378, or the 5-HT3 antagonist, MDL 72222.(ABSTRACT TRUNCATED AT 250 WORDS)
Mitchell
J B
JB
Douglas Hospital Research Center, Department of Psychiatry, McGill University Montreal, Quebec, Canada.
Rowe
W
W
Boksa
P
P
Meaney
M J
MJ
D000818:Animals; D002478:Cells, Cultured; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D011965:Receptors, Glucocorticoid / Q000378:metabolism*; D012701:Serotonin / Q000502:physiology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D013997:Time Factors
D011965:Receptors, Glucocorticoid; D012702:Serotonin Antagonists; D012701:Serotonin