Seasonal variations in morphine withdrawal signs. Prevention with baclofen

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

Jerusalem, Israel

Congreso; Fith Ibro World Congress of Neuroscience; 1999

SEASONAL VARIATIONS IN MORPHINE WITHDRAWAL SIGNS. PREVENTION WITH BACLOFEN.   G.N. Balerio, A.K. Kemmling and 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 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 opioid systems involved in the antinociceptive effect of BAC. On the other hand we have studied the development of MOR antinociceptive tolerance and the cross-tolerance to the BAC effect. Being well known the opioid drugs addiction, the aim of the present study was to examine whether BAC prevents the MOR abstinence signs in mice. 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.). This treatment was performed 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 showed a significant decrease in all the parameters compared with the abstinence group both, in summer and winter. These results suggest that the MOR withdrawal signs in winter are stronger than in summer. The finding that BAC diminished the MOR withdrawal signs suggest that this drug could be useful for the treatment of opioid drugs addiction.