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Paper   IPM / Cognitive Sciences / 8820
School of Cognitive Sciences
  Title:   Morphine-induced place preference: Involvement of cholinergic receptors of the ventral tegmental area
  Author(s): 
1.  A. Rezayof
2.  F. Nazari-Serenjeh
3.  M.R. Zarrindast
4.  H. Sepehri
5.  L. Delphi
  Status:   Published
  Journal: EUR J PHARMACOL
  Vol.:  562
  Year:  2007
  Pages:   92-102
  Supported by:  IPM
  Abstract:
In the present study, the effects of intra-ventral tegmental area injections of cholinergic agents on morphine-induced conditioned place preference were investigated by using an unbiased 3-day schedule of place conditioning design in rats. The conditioning treatments with subcutaneous injections of morphine (0.5? 7.5 mg/kg) induced a significant dose-dependent conditioned place preference for the drug-associated place. Intra-ventral tegmental area injection of an anticholinesterase, physostigmine (2.5 and 5 g/rat) or nicotinic acetylcholine receptor agonist, nicotine (0.5 and 1 g/rat) with an ineffective dose of morphine (0.5 mg/kg) elicited a significant conditioned place preference. Furthermore, intraventral tegmental area administration of muscarinic acetylcholine receptor antagonist, atropine (1?4 g/rat) or nicotinic acetylcholine receptor antagonist, mecamylamine (5 and 7.5 g/rat) dose-dependently inhibited the morphine (5 mg/kg)-induced place preference. Atropine or mecamylamine reversed the effect of physostigmine or nicotine on morphine response respectively. The injection of physostigmine, but not atropine, nicotine or mecamylamine, into the ventral tegmental area alone produced a significant place aversion. Moreover, intraventral tegmental area administration of the higher doses of physostigmine or atropine, but not nicotine or mecamylamine decreased the locomotor activity. We conclude that muscarinic and nicotinic acetylcholine receptors in the ventral tegmental area may critically mediate the rewarding effects of morphine.

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