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 microg/rat) amnesia. The administration of the alpha1-adrenoceptor agonist phenylephrine (0.05 microg/rat) and the alpha1-adrenceptor antagonist prazosin (0.5 microg/rat) did not alter the effect of imipramine. The lower doses of phenylephrine (0.005 and 0.015 microg/rat) impaired, while the higher dose of the drug (0.025 and 0.05 microg/rat) improved retention. The effect of phenylephrine was not altered by prazosin (0.5 and 1 microg/rat) pretreatment, although prazosin alone decreased retention latencies. The alpha2-adrenoceptor antagonist yohimbine (0.5 and 1 microg/rat) decreased the response induced by imipramine. However, the alpha2-adrenoceptor agonist clonidine (0.08 microg/rat) did not alter the effect of the drug. Clonidine (0.15 and 0.3 microg/rat) by itself decreased, while yohimbine (1 and 2 microg/rat) increased retention latencies. Yohimbine pretreatment attenuated the effect of clonidine. It is concluded that alpha2-adrenoceptor mechanism(s) may be involved in imipramine-induced impairment of memory.
Zarrindast
Mohammad Reza
MR
Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran. zarinmr@ams.ac.ir
Ghiasvand
Maryam
M
Homayoun
Houman
H
Rostami
Parvin
P
Shafaghi
Bijan
B
Khavandgar
Simin
S
D018759:Adrenergic Uptake Inhibitors / Q000008:administration & dosage / Q000009:adverse effects*; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000008:administration & dosage / Q000009:adverse effects*; D001362:Avoidance Learning / Q000187:drug effects* / Q000502:physiology; D003000:Clonidine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004597:Electroshock; D006624:Hippocampus / Q000502:physiology; D007099:Imipramine / Q000008:administration & dosage / Q000009:adverse effects*; D008297:Male; D008568:Memory / Q000187:drug effects*; D010656:Phenylephrine / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018340:Receptors, Adrenergic, alpha-1 / Q000187:drug effects; D018341:Receptors, Adrenergic, alpha-2 / Q000187:drug effects*; D015016:Yohimbine / Q000494:pharmacology
D018759:Adrenergic Uptake Inhibitors; D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D000929:Antidepressive Agents, Tricyclic; D018340:Receptors, Adrenergic, alpha-1; D018341:Receptors, Adrenergic, alpha-2; D010656:Phenylephrine; D015016:Yohimbine; D003000:Clonidine; D007099:Imipramine; D011224:Prazosin