Baclofen: Involvement in the prevention of morphine abstinence syndrome in mice

BALERIO GRACIELA N., KEMMLING ALMA K., RUBIO MODESTO C.

Munich, Alemania

Congreso; XIIIth International Congress of Pharmacology; 1998

BACLOFEN: INVOLVEMENT IN THE PREVENTION OF MORPHINE ABSTINENCE SYNDROME IN MICE Graciela Noemi Balerio*, A. K. Kemmling and M. C. Rubio ______________________________________________________ Baclofen (BAC), a selective GABA B agonist, as well as morphine (MOR), a selective opioid agonist, were found to elicit a dose-dependent antinociceptive effect in mice. In previous studies we have demonstrated a possible interaction between the GABAergic and opioidergic systems involved in BAC antinociceptive effect. On the other hand we have studied the development of MOR antinociceptive tolerance and the cross-tolerance to the BAC effect. Being wellkown the opioid drugs addiction, the aim of the present study was to examine the possible participation of BAC in the prevention of MOR abstinence syndrome in mice. All experiments were performed on male Swiss-Webster albino mice weighing 25 to 40 g. Mice were administered with MOR 2 mg/kg via i.p., twice daily for 10 days. After the last dose of the opioid agonist, naloxone (NAL), an opioid antagonist, 6 mg/kg via i.p., was administered and we determined the following signs: explorative locomotion, normal feces, liquid feces, rearing, wet-dog shakes and olfactions. In another group of dependent mice after the last dose of MOR, BAC 2 mg/kg i.p. was administered before NAL-precipitated abstinence and MOR withdrawal signs were measured again. The results clearly demonstrated a significant decrease in all the parameters compared with the abstinence group: explorative locomotion (47.8%, p < 0.01); normal feces (37.5%, p < 0.01); liquid feces (82.2%, p < 0.01); rearing (64.9%, p < 0.01); wet-dog shakes (46.6%, p < 0.01); sniffing (46.2%, p < 0.01). These results suggest that some GABAergic agents might lead to the development of new drugs for treating certain types of drug addiction.    *Cátedra de Farmacología and ININFA (CONICET), Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires. Junín 956, 5º Piso, 1113, Buenos Aires, Argentina.