Imipramine counteracts corticosterone-induced alterations in the effects of the activation of 5-HT(7) receptors in rat hippocampus.
Using extracellular recording we studied changes in the reactivity of rat hippocampal slices to an agonist of the 5-HT(7) receptor, 5-carboxamidotryptamine (5-CT; 0.025-1 microM), induced by an earlier treatment of animals with corticosterone. Spontaneous bursting activity was recorded in ex vivo slices incubated in the presence of 2-[4-(2-methoxyphenyl)-1piperazinyl]ethyl]-N-2-pyridinylcyclohexanecarboxamide (WAY 100635; 2 microM), an antagonist of the 5-HT(1A) receptor, in the medium devoid of Mg2+ ions. Saturation binding assays were performed using [(3)H]-(2R)-1-[(3-hydroxyphenyl)sulfonyl]-2-[2-(4-methyl-1-piperidinyl)ethyl]pyrrolidine hydrochloride (SB 269970), a specific antagonist of the 5-HT(7) receptor. Repetitive, but not single, corticosterone administration lasting 7 and 21 days, resulted in an enhancement of the effect related to the 5-HT(7) receptor activation without changes in its binding properties. In a separate set of experiments rats were treated with corticosterone for 3 weeks and additionally with imipramine, beginning on the eighth day of corticosterone administration. In the corticosterone plus imipramine group the excitatory effect of 5-CT was weaker than in the corticosterone group, indicating that corticosterone-induced functional modifications in the reactivity of the 5-HT(7) receptor were reversed and further weakened by imipramine treatment. This effect was accompanied by a reduction in the density of [3H]-SB 269970 binding sites. Thus, imipramine treatment counteracts the corticosterone-induced increase in the reactivity of the hippocampal circuitry to the activation of the 5-HT(7) receptor.
Tokarski
K
K
Institute of Pharmacology, Polish Academy of Sciences, Krakow, Poland.
Pitra
P
P
Duszynska
B
B
Hess
G
G
D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology*; D001665:Binding Sites; D003345:Corticosterone / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004336:Drug Antagonism; D006624:Hippocampus / Q000187:drug effects* / Q000502:physiology; D007099:Imipramine / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D010636:Phenols / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011985:Receptors, Serotonin / Q000502:physiology*; D012701:Serotonin / Q000031:analogs & derivatives / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D013449:Sulfonamides / Q000494:pharmacology
D000929:Antidepressive Agents, Tricyclic; D010636:Phenols; D010879:Piperazines; D011725:Pyridines; D011985:Receptors, Serotonin; C404922:SB 269970; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D013449:Sulfonamides; C104425:serotonin 7 receptor; D012701:Serotonin; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide; C047087:5-carboxamidotryptamine; D007099:Imipramine; D003345:Corticosterone