Imipramine increases the 5-HT1A receptor-mediated inhibition of hippocampal neurons without changing the 5-HT1A receptor binding.
The effect of repeated treatment with imipramine on the 5-HT1A receptor-mediated inhibition of a population spike was studied in the rat CA1 hippocampal region ex vivo. Serotonin (5-hydroxytryptamine, 5-HT) and the selective 5-HT1A receptor agonist 8-hydroxy-2-(dipropylamino)tetralin (8-OH-DPAT) decreased dose-dependently the amplitude of population spikes; this effect was blocked by the selective 5-HT1A receptor antagonist (S)-N-tert-butyl-3-[4-(2-methoxyphenyl)piperazin-1-yl]-2-phenylpro panamide dihydrochloride [(S)-WAY 100135]. Repeated (14 days, twice daily), but not single, administration of imipramine (10 mg/kg) shifted the dose-response curves for serotonin and 8-OH-DPAT to the left. Repeated treatment with imipramine did not change the density of 5-HT1A receptors in the hippocampus as measured by autoradiography using [3H]8-OH-DPAT as a ligand. The latter findings indicate that the imipramine-induced increase in the responsiveness of hippocampal neurons to stimulation of 5-HT1A receptors may not involve an increase in the density of this receptor subtype. To find out whether the efficacy of the postreceptor transduction mechanism is changed by repeated treatment with imipramine, we examined the effect of baclofen. The baclofen-induced inhibition of the population spike was not changed by imipramine. Our results suggest that repeated treatment with imipramine induces sensitization to the inhibitory effects of 5-HT1A receptor agonists in the hippocampus.
Bijak
M
M
Polish Academy of Sciences, Institute of Pharmacology, Krak-ow, Poland.
Tokarski
K
K
Czyrak
A
A
Maćkowiak
M
M
Wedzony
K
K
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology*; D001345:Autoradiography; D001418:Baclofen / Q000494:pharmacology; D001667:Binding, Competitive; D004558:Electric Stimulation; D018755:GABA Agonists / Q000494:pharmacology; D006624:Hippocampus / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D007099:Imipramine / Q000494:pharmacology*; D008297:Male; D009433:Neural Inhibition / Q000187:drug effects*; D011485:Protein Binding / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D011985:Receptors, Serotonin / Q000032:analysis / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D044263:Receptors, Serotonin, 5-HT1; D012701:Serotonin / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology
D000929:Antidepressive Agents, Tricyclic; D018755:GABA Agonists; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D017366:Serotonin Receptor Agonists; D012701:Serotonin; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D001418:Baclofen; D007099:Imipramine