Adrenoceptor mechanisms underlying imipramine-induced memory deficits in rats

The post-training administration of tricyclic antidepressant imipramine impairs memory consolidation in the passive avoidance task. The present study investigated the effects of intrahippocampal (i.h.) injection of adrenoceptor agents on imipramine-induced (2–8 µg/rat) amnesia. The administration of the α1-adrenoceptor agonist phenylephrine (0.05 µg/rat) and the α1-adrenceptor antagonist prazosin (0.5 µg/rat) did not alter the effect of imipramine. The lower doses of phenylephrine (0.005 and 0.015 µg/rat) impaired, while the higher dose of the drug (0.025 and 0.05 µg/rat) improved retention. The effect of phenylephrine was not altered by prazosin (0.5 and 1 µg/rat) pretreatment, although prazosin alone decreased retention latencies. The α2-adrenoceptor antagonist yohimbine (0.5 and 1 µg/rat) decreased the response induced by imipramine. However, the α2-adrenoceptor agonist clonidine (0.08 µg/rat) did not alter the effect of the drug. Clonidine (0.15 and 0.3 µg/rat) by itself decreased, while yohimbine (1 and 2 µg/rat) increased retention latencies. Yohimbine pretreatment attenuated the effect of clonidine. It is concluded that α2-adrenoceptor mechanism(s) may be involved in imipramine-induced impairment of memory.