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

KEMMLING A., DIAZ S. BALERIO G.

Mendoza

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

Seasonal neurochemical alterations in mice morphine withdrawal syndrome. Prevention with baclofen.  Kemmling A., Diaz S., 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 the present study was to compare the seasonal (summer and winter) changes in levels of biogenic monoamines and its metabolites in various brain regions of male mice during the morphine (MOR) withdrawal syndrome and its prevention with baclofen (BAC). Swiss-Webster albino mice (20-30g) received MOR (2 mg/kg, i.p.), 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 (ST), the cortex (CO ) and the hippocampus (HP) were dissected to determine the endogenous levels of dopamine (DA), 5-hydroxytryptamine (5-HT) and its metabolites using HPLC with electrochemical detection. Summer: 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 it did not in the HVA levels. No differences were observed in the 5-HT concentration between the experimental groups. The DA in the CO of the abstinence group decreased by 63.07% (p<0.05). BAC prevented  the decrease in DA levels. No differences were observed in the 5-HT concentration between the experimental groups. Winter: there were no differences in DA and its metabolites in the ST of the abstinence group while the 5-HT and the 5-HIAA decreased by 31.22% (p<0.001) and 42.01%  (p<0.001) respectively. BAC did not prevent the decrease in 5-HT and 5-HIAA levels. The CO of the abstinence group did not show changes in any of the monoamines and its metabolites. In conclusion, an alteration of dopaminergic and serotoninergic neuron activity in different areas of the brain, would play an important role in the expression of the MOR withdrawal syndrome during the summer and winter respectively.                         Presentación a premio