Imipramine alters beta-adrenergic, but not serotonergic, mediated responses in rat hippocampal pyramidal cells.
Imipramine, a tricyclic antidepressant, acts acutely to block the reuptake of serotonin (5-HT) and norepinephrine (NE). However, imipramine's action as an antidepressant takes several weeks to develop. This study investigated acute and chronic effects of imipramine on intracellularly-recorded responses mediated by 5-HT and beta-adrenergic receptors on pyramidal cells from area CA1 of rat hippocampal slices maintained in vitro. Addition of 10 microM imipramine in the perfusion medium sinistrally shifted the 5-HT1A concentration-response curve for membrane hyperpolarization and the 5-HT concentration-response curve for the reduction in the amplitude of the slow afterhyperpolarization (AHP) elicited by a train of action potentials. After two weeks of treatment with imipramine (10 mg/kg daily i.p. injections or s.c. osmotic mini-pumps) the responses to 5-HT were not altered. In contrast the concentration-response curve for the beta-adrenergic mediated reduction in AHP amplitude was significantly altered; there was a reduction in Emax and a log unit dextral shift in EC50. There was no change in the concentration-response curve for the beta-adrenergic mediated depolarization. These data are in agreement with previous biochemical results reporting a decrease in beta-adrenergic receptor mediated stimulation in adenylyl cyclase and down-regulation of beta-receptor in cortex and hippocampus. These findings suggest that a consequence of long-term imipramine treatment is a decrease in the augmentation of cell excitation normally produced by beta-adrenergic receptor stimulation.
Beck
S G
SG
Department of Pharmacology, Mount Sinai School of Medicine of CUNY, NY 10029.
Halloran
P M
PM
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D007099:Imipramine / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000502:physiology*; D011985:Receptors, Serotonin / Q000502:physiology*
D000929:Antidepressive Agents, Tricyclic; D011943:Receptors, Adrenergic, beta; D011985:Receptors, Serotonin; D007099:Imipramine