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

DIAZ S., KEMMLING A., BALERIO G.

Mendoza

Congreso; XXXII Reunión Anual de Comunicaciones Científicas. XXII Reunión de la Sociedad Farmacológica de Chile.; 2000

Asociación Argentina de Farmacología Experimental

Gender neurochemical alterations in mice morphine withdrawal syndrome. Prevention with baclofen. Diaz S., Kemmling A., Balerio G. Cát. de Farmacología, F F Y B (UBA) ININFA (CONICET), Junín 956 5º piso (1113), Buenos Aires. Email: gbalerio@ffyb.uba.ar   The aim of this study was to compare the changes in levels of biogenic monoamines and its metabolites in various brain regions of male and female mice during the 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 withdrawal. 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 striatum (ST), cortex (CO) and hippocampus (HP) were dissected to determine the endogenous levels of dopamine (DA), 5-hydroxytryptamine (5-HT) and its metabolites using HPLC with electrochemical detection. Male: DA, dihydroxyphenyl acetic acid (DOPAC) and homovanillic acid (HVA) concentrations in the ST of the abstinence group decreased by 49.3% (p<0.001), 67.9% (p<0.01) and 34.2% (p<0.01) respectively. BAC prevented the changes in DA and DOPAC levels, but not in the HVA level. The DA in the CO of the abstinence group decreased by 63.07% (p<0.05). BAC prevented this decrease. No differences were observed in the 5-HT concentration in ST or CO between the experimental groups. There were no differences in any of the monoamines and their metabolites in the HP of the abstinence group. Female: the abstinence group did not show significant changes in any of the monoamines and its metabolites in the three regions studied. These results suggest neurochemical gender differences in the expression of the MOR withdrawal syndrome.