Involvement of D1 and D2 receptors in the attenuation of the morphine withdrawal syndrome in male and female mice

DIAZ S., RUBIO M., BALERIO G.

Corrientes

Congreso; XXXV Reunión Anual de Comunicaciones Científicas.; 2003

Asociación Argentina de Farmacología Experimental

Involvement of D1 and D2 receptors in the attenuation of the morphine withdrawal syndrome in male and female mice. Diaz S, 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 In previous studies, we have found that a significant decrease in striatum and cortical dopamine (DA) levels takes place during MOR withdrawal in male mice but not in females. In order to examine sex differences related to the dopaminergic system, in the present study we evaluated the behavioral effect of two DA selective antagonists SCH 23390 (D1) and raclopride (RAC) (D2) during MOR withdrawal. 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 three groups: withdrawal group received naloxone (NAL, 6 mg/kg, i.p.) after the last dose of MOR in order to precipitate the abstinence syndrome and the other 2 groups received SCH 23390 (0.2 mg/kg, i.p.) or RAC (0.3 mg/kg, i.p.) before NAL injection. After NAL injection, behavioral signs have been recorded for each mice in the open field for 30 minutes. Results have shown that during MOR withdrawal, significant increases in liquid feces, wet dog-shakes and sniffing occur either in male and female mice. When mice were pretreated with SCH 23390 or with RAC, the counts of those three behavioral signs significantly decreased in either sex. The modification of the MOR withdrawal signs by selective DA antagonists, supports the idea that both D1 and D2 receptors play a critical role in the expression of MOR abstinence signs. This finding could be related to the known influence of dopaminergic system on the opiate reward.               Opto premio SAFE