EFFECT OF YOHIMBINE ON THE DEVELOPMENT OF MORPHINE-DEPENDENCE IN THE RAT - LACK OF INVOLVEMENT OF CORTICAL BETA-ADRENOCEPTOR MODIFICATIONS

The alpha 2 receptor antagonist yohimbine has been previously shown to prevent the development of morphine dependence in a rat behavioral mo del. This study was directed to clarify the mechanism of this interact ion, which is presently unknown. Since upregulation of cortical beta-a drenoceptors has been suggested to be involved in morphine withdrawal, we have tested the possible correlation between receptor density and withdrawal behaviors in the presence of yohimbine. Sprague-Dawley male rats received a s.c. suspension of morphine (300 mg/kg) or the vehicl e. Animals received saline or yohimbine (4 mg/kg, IP) 24, 28, 48 and 5 2 h after morphine and finally naloxone (1 mg/kg i.p) at 72 h; the sub sequent signs of withdrawal (mainly wet-dog shakes and escape attempts ) were recorded and the cerebral cortex dissected to study [H-3]-CGP 1 2177 binding. Morphine-treated animals displayed a marked withdrawal b ehavior together with beta-adrenoceptor upregulation; nevertheless, th ese effects were not correlated. As expected, yohimbine prevented morp hine withdrawal behavior but did nor reverse the beta-adrenoceptor upr egulation induced by the opiate. These results confirm previous eviden ce against the involvement of beta-adrenoceptor upregulation on morphi ne withdrawal behaviors and also permit to discard beta-adrenoceptor r egulation as the neurochemical basis of the antiwithdrawal effect of y ohimbine. The possible contribution of some other neurochemical effect s of yohimbine are discussed to explain the inhibition of morphine dep endence by that drug. Copyright (C) 1997 Elsevier Science Inc.