Imipramine counteracts corticosterone-induced alterations in the effects of the activation of 5-HT(7) receptors in rat hippocampus

K Tokarski, P Pitra, B Duszynska, G Hess
2009 Journal of Physiology and Pharmacology  
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
more » ... 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.
pmid:19617650 fatcat:bubfasprpffaneyavswfiw4xty