Mutant mice lacking the cholecystokinin(2) receptor show a dopamine-dependent hyperactivity and a behavioral sensitization to morphine

Cholecystokinin(2) (CCK2) receptor-deficient mice were used to analyze the in vivo function of CCK2 receptor and especially the incidence of this gene invalidation on enkephalinergic and dopaminergic systems. Hyperlocomotor a ctivity of CCK2 receptor-deficient mice was suppressed by a selective D2 an tagonist but not by a D1 antagonist. Injection of amphetamine induced a hyp erlocomotor activity in both groups of mice while mutant mice were less sen sitive to cocaine. Administration of 6 mg/kg of morphine once every 2 days for 5 days significantly (P < 0.05) enhanced motor activity the last day co mpared to the first day, only in CCK2 receptor-deficient mice. These result s emphasize the role of CCK2 receptors in counteracting the effects of dopa minergic systems and suggest that CCK2 receptor invalidation could lead to a slight behavioral sensitization. (C) 2001 Elsevier Science Ireland Ltd. A ll rights reserved.