NMDA glutamate but not dopamine antagonists blocks drug-induced reinstatement of morphine place preference.
The effects of dopaminergic and glutamatergic antagonists on the drug-induced reinstatement of a previously extinguished morphine conditioned place preference (CPP) in mice were evaluated. Following extinction of a place preference induced by morphine (40 mg/kg), a non-contingent injection of the dopaminergic antagonists SCH 23390 (0.125, 0.5 mg/kg), raclopride (0.3, 1.2 mg/kg), haloperidol (0.1, 0.2 mg/kg) and the dopamine (DA) release inhibitor CGS 10746B (1, 10 mg/kg) or glutamatergic NMDA antagonists memantine (10, 20, 40 mg/kg) and MK-801 (0.1, 0.2, 0.3 mg/kg) alone or with 10 mg/kg morphine was given. Neither the dopaminergic nor the glutamatergic antagonists alone reinstated the place preference. Dopamine antagonists failed to block the morphine-induced reinstatement of place preference while memantine and MK-801 blocked it with intermediate and high doses. These results suggest that drug-induced reinstatement of place preference may be largely independent of dopamine and more closely related to glutamatergic neurotransmission.
Ribeiro Do Couto
B
B
Departamento de Psicobiología, Facultad de Psicología, Universitat de Valencia, Avda. Blasco Ibáñez, 21 46010 Valencia, Spain.
Aguilar
M A
MA
Manzanedo
C
C
Rodríguez-Arias
M
M
Miñarro
J
J
D000701:Analgesics, Opioid / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D003216:Conditioning, Operant / Q000187:drug effects*; D018492:Dopamine Antagonists / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D005108:Extinction, Psychological / Q000187:drug effects; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009020:Morphine / Q000494:pharmacology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*
D000701:Analgesics, Opioid; D018492:Dopamine Antagonists; D018691:Excitatory Amino Acid Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D009020:Morphine