Gender-related neurochemical alterations in mice morphine withdrawal syndrome. Prevention with baclofen

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

New Orleans, Los Angeles, USA

Congreso; 30th Annual Meeting Society for Neuroscience; 2000

GENDER-RELATED NEUROCHEMICAL ALTERATIONS IN MICE MORPHINE WITHDRAWAL SYNDROME. PREVENTION WITH BACLOFEN. G.N. Balerio*, S.L. Diaz, A.K. Kemmling, C.G. Bonelli and M.C. Rubio.  Cátedra de Farmacología, Universidad de Buenos Aires and ININFA (CONICET), Junín 956 5º piso, 1113, Buenos Aires, Argentina.    The aim of the present study was to compare the changes in levels of biogenic monoamines and their metabolites in various brain regions of male and female mice during the MOR withdrawal syndrome and its prevention with baclofen (BAC). Swiss-Webster albino male and female 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. 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. The DA, the dihydroxyphenyl acetic acid (DOPAC) and the homovanillic acid (HVA) concentrations in the striatum of the male abstinence group decreased by 49.3% (p<0.001), 67.9% (p<0.01) and 34.2% (p<0.01) respectively. 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, 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 male abstinence group decreased by 63.07% (p<0.05). In the group pretreated with BAC, the DA increased by 198.2% (p<0.05), but no changes were observed in their metabolites (DOPAC and HVA) and in the 5-HT and 5-HIAA concentrations. There were no differences in any of the monoamines and their metabolites in the hippocampus of the male abstinence group. The female mice did not show changes in any of the monoamines and their metabolites in the three regions studied. These results suggest the existence of important gender neurochemical differences in the MOR withdrawal syndrome.    Supported by Grant JB32 from University of Buenos Aires.