Striatal mu-opioid receptor changes during morphine withdrawal in mice

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

Tandil

Congreso; XXXIV Reunión Anual de Comunicaciones Científicas.; 2002

Asociación Argentina de Farmacología Experimental

Striatal m-opioid receptor changes during morphine withdrawal in mice. Diaz S, Kemmling A, Bonavita C, Rubio M, Balerio G. Cát. de Farmacología, FFYB (UBA) e ININFA (CONICET), Junín 956 5º piso (1113), Buenos Aires. e-mail: gbalerio@ffyb.uba.ar Behavioral and neurochemical sex differences have been shown during the morphine (MOR) withdrawal syndrome in mice. In the present study we evaluated striatal m-opioid receptor binding parameters in male and female mice, during MOR withdrawal and after its prevention with the GABAB agonist, baclofen (BAC). Swiss-Webster mice (27-33g) were rendered dependent by i.p. injection of MOR (2 mg/kg), twice daily for 9 days. On the 10th day, dependent mice were divided into two groups: withdrawal group received naloxone (NAL, 6 mg/kg, i.p.) after the last dose of MOR in order to precipitate the abstinence syndrome, while prevention group received BAC (2 mg/kg, i.p.) before NAL injection. After these treatments mice were killed and binding of [3H]-DAMGO to m-opioid receptors was performed. Results (mean ± SEM) were as follow: MALE                               FEMALE                                  Kd             Bmax                  Kd             Bmax Saline control   1.2 ± 0.1     159.8 ± 4.7       1.1 ± 0.1     170.4 ± 4.3 Withdrawal      1.3 ± 0.2     306.6 ± 13.2*    1.2 ± 0.3    180.2 ± 9.2 Prevention       2.8 ± 0.9*   255.5 ± 31.1*     1.5 ± 0.3    172.6 ± 8.0 Significant changes occur in male striatum during MOR withdrawal and after pretreatment with BAC. On the contrary, no alterations in affinity or density of m-binding sites occur in females. These results suggest that pharmacological sex differences in the expression of MOR withdrawal would be related to changes in striatal m-opioid receptor characteristics.             OPTO POR EL PREMIO SAFE