Neurochemical variations in the morphine withdrawal síndrome. Prevention with baclofen

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

Florencia, Italia

Conferencia; VII World Conference on Clinical Pharmacology and Therapeutics- IUPHAR- División of Clinical Pharmacology. 4th Congress of the European Association for Clinical Pharmacology and Therapeutics.CPT 2000; 2000

NEUROCHEMICAL VARIATIONS IN THE MORPHINE WITHDRAWAL SYNDROME. PREVENTION WITH BACLOFEN. A.K. Kemmling, S.L. Diaz, C.G. Bonelli and G.N. Balerio Cátedra de Farmacología, University of Buenos Aires and ININFA (CONICET). Buenos Aires, Argentina.   The aim of this study was to analyze the neurochemical variations during the morphine (MOR) withdrawal syndrome and its prevention with baclofen (BAC). Swiss-Webster albino male mice (20-30g) received MOR (2mg/kg, i.p.), twice daily for 10 days. This pool of dependent animals was divided into two groups: one of them, after the last dose of MOR, received the opioid antagonist naloxone (NAL) (6 mg/kg, i.p.) to precipitate the abstinence syndrome. Another group of dependent mice, received BAC (2mg/kg, i.p.) before NAL-precipitated abstinence. Ten minutes after this treatment, mice mwere sacrificed and the striatum was dissected to determine the endogenous levels of dopamine (DA), its metabolites and 5-hydroxytryptamine (5-HT) using HPLC-coupled electrochemical detection. The DA, the dihydroxyphenyl  acetic acid (DOPAC) and the homovanillic acid (HVA) concentrations in the abstinence group decreased by 49,3% (p<0,001), 67,9% (p<0.01) and 34.2% (p<0.01) respectively 1vs the control group, while in the group pretreated with BAC, the DA and DOPAC levels increased by 51,2% (p<0.05) and 145,6% (p<0.01) respectively vs the abstinence group, but there were no differences in the HVA level. There were no differences in the 5-HT concentration between the control, abstinence and prevention groups. These results suggest that changes in DA levels and its metabolites would be related with a decrease in the activity of the striatal dopamine neurons during the MOR withdrawal syndrome, while the 5-HT striatal levels wouldn’t be modified in this syndrome. BAC would have a tendency to reestablish the activity of the DA neurons decreased in the MOR withdrawal syndrome.         Corresponding author: Graciela Balerio Address: Facultad de Farmacia y Bioquímica, Cátedra de Farmacología (UBA), Junín 956, 5º piso (1113), Buenos Aires, Argentina. TEL: 54-11-4961-5949 FAX: 54-11-4963-8593 e-mail: gbalerio@huemul.ffyb.uba.ar                                                                                                                                                                                                                                                                                               A.5 Drug dependence.