Modulation of the 5-hydroxytryptamine4 receptor-mediated response by short-term and long-term administration of corticosterone in rat CA1 hippocampal pyramidal neurons.
Corticosterone (CT) treatment decreases the magnitude of the 5-hydroxytryptamine (5-HT)1A receptor-mediated hyperpolarization in rat CA1 hippocampal pyramidal neurons. In the present study, we examined the short- and long-term effects of CT on the functionally excitatory 5-HT4 receptor-mediated decrease in the amplitude of the slow afterhyperpolarization (sAHP) that follows a calcium spike and the concomitant decrease in sAHP half decay time. Rats were adrenalectomized (ADX) 2 weeks before the experiment. Data for concentration-response curves were obtained with sharp electrode current clamp recordings in the CA1 pyramidal cell layer of hippocampal slices. Significant changes were found in the 5-HT4 receptor-mediated decrease in sAHP amplitude. The Emax of the 5-HT4 response was significantly increased in cells from ADX rats when the superfusion medium contained 1 nM CT. Short-term administration of 100 nM CT did not alter the 5-HT4 response. Chronic treatment with low concentrations of CT decreased the Emax of the 5-HT4 response. Treatment with CT concentrations that mimic conditions of chronic stress decreased the Emax of the 5-HT4 response and shifted the EC50 to the right. Based on these results we conclude that the magnitude and the potency of the 5-HT4 receptor-mediated decrease in sAHP amplitude is altered by CT. Because the short- and long-term effects of CT treatment are not the same, the actions of CT are time and concentration dependent. CT modulation of the 5-HT4 response is different from its modulation of the 5-HT1A response.
Birnstiel
S
S
Department of Pharmacology, Loyola University Medical Center, Maywood, Illinois, USA.
Beck
S G
SG
D000200:Action Potentials; D000818:Animals; D003345:Corticosterone / Q000494:pharmacology*; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D066298:In Vitro Techniques; D008297:Male; D017966:Pyramidal Cells / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000187:drug effects* / Q000502:physiology
D011985:Receptors, Serotonin; D003345:Corticosterone