Imipramine but not 5-HT(1A) receptor agonists or neuroleptics induces adaptive changes in hippocampal 5-HT(1A) and 5-HT(4) receptors.
It has been reported that the treatment with a tricyclic antidepressant imipramine induces an increase in the sensitivity of 5-HT(1A) receptors and a decrease in the sensitivity of 5-HT(4) receptors in the rat hippocampus. 5-HT(1A) receptor agonists and neuroleptics also affect 5-HT(1A) receptors in different brain areas; therefore, it was of interest to compare their effects on hippocampal 5-HT receptors with the influence of the well-established antidepressant imipramine. We studied the effects of repeated treatment with imipramine, the 5-HT(1A) receptor agonists 8-hydroxy-2(di-n-propylamino)tetralin (8-OH-DPAT) and buspirone, and the neuroleptics haloperidol and clozapine on the sensitivity of rat hippocampal CA1 neurons to 5-HT(1A)- and 5-HT(4) receptor activation. Imipramine was administered for 21 days (10 mg/kg p.o., twice daily), 8-OH-DPAT for 7 days (1 mg/kg s.c., twice daily) and buspirone for 21 days (5 mg/kg s.c., twice daily). The rats received haloperidol (1 mg/kg) and clozapine (30 mg/kg) for 6 weeks in drinking water. Hippocampal slices were prepared 2 days after the last treatment with imipramine, 8-OH-DPAT or buspirone, and 5 days after the last treatment with the neuroleptics. Using an extracellular in vitro recording, we studied changes in the amplitude of stimulation-evoked population spikes, induced by 5-HT, 8-OH-DPAT and the 5-HT(4) receptor agonist zacopride. Activation of 5-HT(1A) receptors decreased, while activation of 5-HT(4) receptors increased the amplitude of population spikes. Imipramine significantly enhanced the inhibitory effects of 5-HT and 8-OH-DPAT, and attenuated the excitatory effect of zacopride. No other treatment used in the present study changed the sensitivity of hippocampal CA1 neurons to 5-HT(1A) and 5-HT(4) receptors activation. These findings indicate that adaptive changes in the sensitivity of hippocampal neurons to 5-HT(1A) and 5-HT(4) receptors agonists are specific to imipramine and may thus-at least partly-mediate its effects.
Zahorodna
Agnieszka
A
Department of Physiology, Institute of Pharmacology, Polish Academy of Sciences, Smetna 12, 31-343, Cracow, Poland. zahoro@if-pan.krakow.pl
Tokarski
Krzysztof
K
Bijak
Maria
M
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001549:Benzamides / Q000494:pharmacology; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology; D003024:Clozapine / Q000494:pharmacology; D006220:Haloperidol / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D007099:Imipramine / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D011985:Receptors, Serotonin / Q000187:drug effects*; D044263:Receptors, Serotonin, 5-HT1; D044422:Receptors, Serotonin, 5-HT4; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*
D000928:Antidepressive Agents; D014150:Antipsychotic Agents; D001549:Benzamides; D019086:Bridged Bicyclo Compounds, Heterocyclic; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D044422:Receptors, Serotonin, 5-HT4; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; C055971:zacopride; D003024:Clozapine; D006220:Haloperidol; D007099:Imipramine