INHIBITION OF MORPHINE-WITHDRAWAL BY LAMOTRIGINE - INVOLVEMENT OF NITRIC-OXIDE

We studied the effects of lamotrigine 3,5-diamino-6-(2,3-dichloropheny l)-1,2,4-triazine] a new antiepileptic compound, on naloxone-precipita ted morphine withdrawal in mice. Pretreatment with lamotrigine (5-100 mg/kg, s.c.) reversed in a dose-dependent way the withdrawal-induced i ncrease in cerebellar Ca2+-dependent nitric oxide (NO) synthase activi ty and reduced the number of escape jumps and other motor symptoms of abstinence, at doses that did not modify locomotor activity (25-50 mg/ kg). Pretreatment with the NMDA receptor antagonist MK-801 [(+)-5-meth yl-10,11-dihydroxy-5H-dibenzor [a,d]cyclohepten-5,10-imine; dizocilpin e] (0.1-0.3 mg/kg, s.c.) also reversed the increase in cerebellar Ca2-dependent NO synthase activity. However, although MK-801 reduced the number of escape jumps and other motor symptoms of abstinence, its eff ects were not clearly dose-dependent. Furthermore, the highest dose of MK-801 tested (0.3 mg/kg) caused an impairment of the locomotor behav iour in naive mice. Thus, lamotrigine may represent a new and useful a gent for the treatment of opiate abstinence.