The amygdala modulates morphine-induced state-dependent memory retrieval via muscarinic acetylcholine receptors.
The current study was conducted to examine the involvement of muscarinic acetylcholine receptors of the amygdala in morphine-induced state-dependent memory retrieval. Male Wistar rats implanted bilaterally with cannulas in the amygdala were submitted to a step-through type passive avoidance task, and tested 24 h after training to measure step-through latency. Post-training s.c. administration of morphine at the doses of 5 and 7.5 mg/kg impaired the memory on the test day, which was restored when the same doses of morphine were used as a pre-test drug. This phenomenon is well known as morphine-induced state-dependent memory retrieval. Bilateral microinjection of the non-selective muscarinic acetylcholine receptor agonist, pilocarpine (0.25 and 0.5 microg/side), into the amygdala with an ineffective dose of morphine (0.5 mg/kg s.c.) significantly improved the memory retrieval and mimicked the effects of pre-test administration of a higher dose of morphine. It should be noted that in the animals that received saline after training and tested following intra-amygdala administration of pilocarpine (0.125, 0.25 and 0.5 microg/side) and those which received post-training morphine (7.5 mg/kg s.c.) and pre-test intra-amygdala microinjection of the same doses of pilocarpine, no significant change was observed in the step-through latencies. On the other hand, pre-test intra-amygdala microinjection of a selective muscarinic acetylcholine receptor antagonist scopolamine (0.125 and 0.25 microg/side) inhibited morphine-induced state-dependent memory retrieval. In addition, no significant changes were seen in memory retrieval of the animals trained before saline treatment and tested following intra-amygdala microinjection of the same doses of scopolamine (0.0625, 0.125 and 0.25 microg/side). Bilateral microinjection of scopolamine into the amygdala reversed the pilocarpine-induced potentiation of the morphine response. In view of the known actions of the drugs used, the present data point to the involvement of amygdala muscarinic acetylcholine receptors in morphine-induced state-dependent memory retrieval.
Rezayof
A
A
Department of Animal Biology, School of Biology, College of Science, University of Tehran, Enghelab Avenue, PO Box 4155-6455, Tehran, Iran. rezayof@khayam.ut.ac.ir
Khajehpour
L
L
Zarrindast
M R
MR
D000679:Amygdala / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D001245:Association Learning / Q000187:drug effects; D001362:Avoidance Learning / Q000187:drug effects; D001522:Behavior, Animal / Q000187:drug effects; D003214:Conditioning, Classical / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D008297:Male; D011939:Mental Recall / Q000187:drug effects*; D008845:Microinjections; D009020:Morphine / Q000494:pharmacology*; D018727:Muscarinic Antagonists / Q000494:pharmacology; D009294:Narcotics / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000378:metabolism*; D012153:Retention, Psychology / Q000187:drug effects; D012601:Scopolamine / Q000494:pharmacology
D018727:Muscarinic Antagonists; D009294:Narcotics; D011976:Receptors, Muscarinic; D009020:Morphine; D012601:Scopolamine