Morphine withdrawal syndrome and prevention with baclofen: changes in monoamines and their metabolites levels in different areas of the brain

RUBIO M., KEMMLING A., DIAZ S., BONELLI C., BALERIO G

Sao Paulo, Brazil

Congreso; XVI Latinamerican Congress of Pharmacology. XXXII Brazilian Congress of Pharamcology and Experimental Therapeutics. II Iberoamerican Congress of Pharmacology. VII Interamerican Congress of Clinical Pharmacology and Therapeutics; 2000

MORPHINE WITHDRAWAL SYNDROME AND PREVENTION WITH BACLOFEN: CHANGES IN MONOAMINES AND THEIR METABOLITES LEVELS IN DIFFERENT AREAS OF THE BRAIN. Rubio, M., Kemmling, A., Diaz, S., Bonelli, C., Balerio, G., Cátedra de Farmacología, Universidad de Buenos Aires and ININFA (CONICET), Junín 956 5º piso, 1113, Buenos Aires, Argentina. INTRODUCTION AND GOALS In previous studies we have characterized the behavioral signs of the morphine (MOR) withdrawal syndrome and its prevention with baclofen (BAC) in mice. The aim of this study was to analyze the neurochemical variations in various brain regions of mice during the MOR withdrawal syndrome and its prevention with BAC. METHODS Swiss-Webster albino male mice (20-30g) received MOR (2 mg/kg, i.p.), twice daily for 10 days. After the last dose of MOR, a group of dependent animals received the opioid antagonist naloxone (NAL) (6 mg/kg, i.p.) in order to precipitate the abstinence syndrome. Another group of dependent mice, received BAC (2 mg/kg, i.p.) before NAL-precipitated abstinence (prevention group). Ten minutes after this treatment, mice were sacrificed and the striatum, the cortex and the hippocampus were dissected to determine the endogenous levels of dopamine (DA), 5-hydroxytryptamine (5-HT) and its metabolites using high-performance liquid chromatography with electrochemical detection. RESULTS The DA, the dihydroxyphenyl acetic acid (DOPAC) and the homovanillic acid (HVA) concentrations in the striatum of the abstinence group decreased by 49.3% (p<0.001), 67.9% (p<0.01) and 34.2% (p<0.01) respectively. In the prevention group, the DA and DOPAC levels increased by 51.2% (p<0.05) and 145.6% (p<0.01) respectively, but there were no differences in the HVA level. No differences were observed in the 5-HT concentration between the experimental groups. The DA in the cortex of the abstinence group decreased by 63.07% (p<0.05) while in the prevention group, the DA increased by 198.2% (p<0.05). No changes were observed either in the DOPAC and HVA or in the 5-HT and 5-HIAA concentrations. There were no differences in any of the monoamines and its metabolites in the hippocampus of the abstinence group.     CONCLUSION These results suggest that an alteration of dopaminergic neuron activity following a reduction of DA and its metabolites in specific brain regions play an important role in the expression of the opioid withdrawal syndrome. BAC would reestablish the activity of the DA neurons decreased in the MOR withdrawal syndrome.           Area de resúmen: 1. Neurociencia y Comportamiento