Interactive Effects of Acute and Chronic Lithium with Dopamine Receptor Antagonists on Naloxone-Induced Jumping in Morphine-Dependent Mice

Abstract

In the present study, interactive effects of D1 and D2 dopamine receptors antagonists and different periods of lithium pretreatment on morphine dependence in mice have been investigated. This study was designed to investigate whether the hypothesis that lithium and dopaminergic mechanisms via their effects on phosphoinositide pathways and calcium flux could influence morphine withdrawal response as manifested in the jumping effect. Animals were treated subcutaneously with morphine (50, 50 and 75 mg/kg) three times daily (10 a.m., 1 p.m. and 4 p.m.) for 3 days, and a last dose of morphine (50 mg/kg) was administered on the 4th day. Withdrawal syndrome (jumping) was precipitated by naloxone (5 mg/kg) which was administered intraperitoneally 2h after the last dose of morphine. To study interactive effects of dopamine receptor antagonists and different duration of lithium pretreatment, 10 injection of morphine (3 administrations each day) for dependence and a dose of 5 mg/kg of naloxone for withdrawal induction were employed. SCH 23390 (0.01, 0.02 and 0.05 mg/kg) as a D1 dopamine receptor antagonist and sulpiride (20, 40 and 80 mg/kg) as a D2 dopamine receptor antagonist were able to prevent withdrawal signs precipitated by naloxone (5 mg/kg). Pretreatment of animals with lithium (600 mg/l) for 7, 14, 21 and 28 days, increased jumping induced by naloxone in morphine dependent animals. SCH 23390 did not show any significant alteration on the jumping response in animals pretreated with lithium for 28 days, but the inhibitory effects of sulpiride was significantly decreased in animals received lithium for 28 days. It is concluded that postreceptor mechanism (s) may be involve in the interactions of lithium with dopaminergic system in alteration of naloxone-induced jumping in morphine dependent animals.