title: Modulation of morphine state-dependent learning by muscarinic cholinergic receptors of the ventral tegmental area.
abstract: In the present study, the effects of bilateral intra-ventral tegmental area (intra-VTA) injections of an anticholinesterase, physostigmine and/or muscarinic acetylcholine receptor antagonist, atropine on memory retention and morphine state-dependent learning were examined in adult male Wistar rats. As a model of learning, a step-through passive avoidance task was used. Post-training subcutaneous administration of morphine (0.5, 2.5 and 5 mg/kg) dose-dependently impaired memory retrieval on the test day. Pre-test administration of morphine (2.5 and 5 mg/kg) induced state-dependent retrieval of the memory acquired under post-training morphine influence. Pre-test intra-VTA microinjection of physostigmine (0.5, 1 and 2 microg/rat) or atropine (1, 2 and 3 microg/rat) alone cannot affect memory retention. Interestingly, pre-test intra-VTA administration of physostigmine (1 and 2 microg/rat) reversed post-training morphine (5 mg/kg, s.c.)-induced retrieval impairment. Furthermore, pre-test intra-VTA microinjection of physostigmine (1 and 2 mug/rat) with an ineffective dose of morphine (0.5 mg/kg), synergistically improved memory performance impaired by post-training morphine. On the other hand, pre-test intra-VTA microinjection of atropine (2 and 3 microg/rat) 5 min before the administration of morphine (5 mg/kg, s.c.) dose-dependently inhibited morphine state-dependent memory. Pre-test atropine microinjection also reversed the influence of physostigmine on morphine response. It may be concluded that the muscarinic acetylcholine receptors of the VTA play an important role in morphine-induced recovery of memory, on the test day.
authors.affiliation: Department of Animal Biology, School of Biology, College of Science, University of Tehran, Tehran, Iran.
authors.forename: Niloufar
authors.initials: N
authors.lastname: Darbandi
authors.forename: Ameneh
authors.initials: A
authors.lastname: Rezayof
authors.forename: Mohammad-Reza
authors.initials: MR
authors.lastname: Zarrindast
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001285:Atropine / Q000008:administration & dosage; D001362:Avoidance Learning / Q000187:drug effects*; D001522:Behavior, Animal / Q000187:drug effects; D002800:Cholinesterase Inhibitors / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004347:Drug Interactions; D008297:Male; D008568:Memory / Q000187:drug effects; D008845:Microinjections; D009020:Morphine / Q000494:pharmacology*; D018727:Muscarinic Antagonists / Q000008:administration & dosage; D009294:Narcotics / Q000494:pharmacology*; D010830:Physostigmine / Q000008:administration & dosage; D051381:Rats; D017208:Rats, Wistar; D011976:Receptors, Muscarinic / Q000187:drug effects*; D012153:Retention, Psychology / Q000187:drug effects*; D017557:Ventral Tegmental Area / Q000187:drug effects*
chemical_list: D002800:Cholinesterase Inhibitors; D018727:Muscarinic Antagonists; D009294:Narcotics; D011976:Receptors, Muscarinic; D009020:Morphine; D001285:Atropine; D010830:Physostigmine