Seasonal and gender variations in morphine withdrawal signs. Prevention with baclofen

BALERIO G.N., KEMMLING A.K. DIAZ S.L. AND M.C. RUBIO

Miami, Florida, USA

Conferencia; GABAB Receptors. The 8th Neuropharmacology Conference. An Official Satellite of the 1999 Meeting of the Society for Neuroscience; 1999

SEASONAL AND GENDER VARIATIONS IN MORPHINE WITHDRAWAL SIGNS. PREVENTION WITH BACLOFEN.   Balerio G.N.*, Kemmling A.K., Diaz S.L., M.C. Rubio Cátedra de Farmacología, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires & Instituto de Investigaciones Farmacológicas (CONICET). Buenos Aires, Argentina.       Baclofen (BAC), a selective GABAB 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 opioid systems involved in the antinociceptive effect of BAC. The aim of the present study was to examine the seasonal and gender variations in the MOR abstinence syndrome in mice and the possible participation of BAC in the prevention of that syndrome. The experiments were performed in two seasons (summer and winter) on male Swiss-Webster albino mice weighing 25 to 35 g. Mice received MOR (2 mg/kg, i.p.), twice daily for 10 days. After the last dose of the opioid agonist, naloxone (NAL) (6 mg/kg, i.p.), an opioid antagonist, was administered and the following signs were determined: locomotor activity, normal feces, liquid feces, rearing, wet-dog shakes and sniffing. In a group of MOR dependent mice, the last dose of MOR was followed by the administration of BAC (2 mg/kg, i.p.) before the NAL-precipitated abstinence syndrome. In winter the results showed a significant increase in certain morphine abstinence signs compared with the summer group: liquid feces (65.25 %, p<0.001); wet-dog shakes (46.1 %, p<0.01); sniffing (35.34 %, p<0.001). BAC administration before NAL-precipitated abstinence syndrome produced a significant decrease in all the parameters compared with the abstinence group, in summer as well as in winter. The sexual study was performed in winter and only two parameters of the MOR abstinence syndrome were found in female mice. The results showed a significant increase in wet-dog shakes ( 72.38 %, p<0.001) in male compared with female mice. These results suggest that in winter, the MOR withdrawal signs are stronger than in summer. Female would be less sensitive than male mice to develop the MOR abstinence syndrome. The finding that BAC diminished the MOR withdrawal signs suggest that this drug could be useful for the treatment of drug withdrawal symptoms.        Keywords: seasonal variations gender variations morphine withdrawal baclofen         I declare that the material will not be presented prior to the Conference. NAME: GRACIELA NOEMI BALERIO ADDRESS: Facultad de Farmacia y Bioquímica, Cátedra de Farmacología, Universidad de Buenos Aires, Junín 956, 5º Piso, (1113), Buenos Aires, Argentina. PHONE: 54-11-4961-5949            FAX: 54-11-4963-8593 e-mail: gbalerio@huemul.ffyb.uba.ar