Effects of CGS 10746B on hyperactivity and place preference induced by morphine.
The effects of CGS 10746B, a dopamine release inhibitor, on spontaneous locomotor activity, morphine-induced hyperactivity, acquisition of conditioned place paradigm and morphine-induced conditioned place preference (CPP) was evaluated in male mice. In experiment 1, animals treated with CGS 10746B (0.5, 1, 2, 4, 8, 16, 24 and 32 mg/kg), morphine (40 mg/kg) or morphine (40 mg/kg) plus CGS 10746B (0.5, 1, 2, 4, 8, 16, 24 and 32 mg/kg) were placed in an actimeter during a period of 90 min. In experiment 2, animals treated with CGS 10746B (0.5, 1, 3 and 10 mg/kg), morphine (40 mg/kg) or morphine (40 mg/kg) plus CGS 10746B (0.5, 1, 3 and 10 mg/kg) were conditioned following a procedure unbiased in terms of initial spontaneous preference. In experiment 1, it was found that a decrease in spontaneous locomotor activity was produced between 0 and 45 min after administration of 24 and 32 mg/kg of CGS 10746B. In contrast, morphine induced hyperactivity between 45 and 90 min after administration. CGS 10746B reduced morphine-induced hyperactivity with doses of 2 mg/kg and higher. In experiment 2, CGS 10746B did not produce any effect on place conditioning but blocked morphine-induced CPP with doses from 1 mg/kg upwards. Our results confirm that an intact dopamine neurotransmission is critical for the manifestation of the motor and place preference conditioning effects of morphine.
Manzanedo
C
C
Area de Psicobiología, Facultad de Psicología, Universitat de Valencia, Aptdo. 22109, 46071 Valencia, Spain.
Serrano
A
A
Aguilar
M A
MA
Rodríguez-Arias
M
M
Miñarro
J
J
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001245:Association Learning / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000502:physiology; D002755:Choice Behavior / Q000187:drug effects*; D003214:Conditioning, Classical / Q000187:drug effects*; D004298:Dopamine / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009020:Morphine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D012931:Social Environment; D013841:Thiazepines / Q000494:pharmacology*
D014150:Antipsychotic Agents; D013841:Thiazepines; D009020:Morphine; C049819:CGS 10746B; D004298:Dopamine