Changes in cortical m-opioid receptor binding in morphine withdrawal in mice

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

Corrientes

Congreso; XXXV Reunión Anual de Comunicaciones Científicas.; 2003

Asociación Argentina de Farmacología Experimental

Changes in cortical m-opioid receptor binding in morphine withdrawn mice.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 We have previously demonstrated sex differences in whole brain and striatal m-opioid receptor binding parameters during the morphine (MOR) withdrawal syndrome in mice. In this study, we evaluated cortical m-opioid receptor binding in male and female mice, during MOR withdrawal and its prevention with the GABAB agonist, baclofen (BAC). Swiss-Webster mice (24-27g) 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, prefrontal cortex was disected and binding of [3H]-DAMGO to m-opioid receptors was performed. A significant increase in cortical m-opioid receptor density occur during MOR withdrawal in either sex, but no alterations in affinity of m-binding sites occur in males nor in females. In prevention groups, no differences have been shown, neither in density nor in affinity, compared with the control groups. Our results indicate that cortical m-opioid receptor upregulation observed during the NAL-precipitated withdrawal occur in either sex. Considering that prefrontal cortex is involved in the reward system, a possible mechanism intending to compensate the blockade of m-opioid receptors is developped similarly in males and females.