ON THE MECHANISM(S) OF CHOLECYSTOKININ (CCK) - RECEPTOR STIMULATION ATTENUATES MORPHINE-DEPENDENCE IN MICE

In the present study, effect of cholecystokinin (CCK) agonists and on dependence to morphine in mice has been investigated. The influence of dopaminergic, adrenergic, cholinergic and serotonergic on attenuation of naloxone-induced jumping in morphine-dependent mice by CCK agonist s were also considered. Mice were treated subcutaneously with morphine (50, 50 and 75 mg/kg) three times daily (10 a.m. 1 p.m. and 4 p.m.) f or 3 days, and a last dose of morphine (50 mg/kg) was administered on the 4th day. Withdrawal syndrome (jumping) was precipitated by naloxon e (5 mg/kg) which was administered intraperitoneally 2 hr after the la st dose of morphine. To study effects of CCK receptor agonists, 10 inj ection of morphine (3 administrations each day) for dependence and a d ose of 5 mg/kg of naloxone for withdrawal induction were employed. The CCK agonists CCK-8 (0.001-0.1 mg/kg), unsulfated CCK-8 (CCK-8U; 0.001 -0.1 mg/kg) and caerulein (0.00001-0.01 mg/kg) were able to prevent wi thdrawal signs precipitated by naloxone (5 mg/kg). Sulpiride and pimoz ide increased response induced by CCK-8 agonists. The dopamine antagon ists also attenuates jumping by themselves. SCH 23390 did not alter th e CCK-8 effect, but decreased the jumping by itself. Phenoxybenzamine, propranolol, methysergide and atropine did not change the caerulein e ffect significantly. However, single administration of atropine increa sed and methysergide decreased jumping. It is concluded that CCK mecha nism(s) may be involved in morphine dependence, and dopaminergic mecha nism(s) may interact with CCK in attenuation of naloxone-induced jumpi ng.