Role of beta-adrenoceptors in the expression of morphine withdrawal signs.

The effects of intracerebroventricular (i.c.v.) pretreatment with the noradrenergic neurotoxin DSP-4 and beta 1- and beta 2-adrenoceptor antagonists on the expression of morphine withdrawal signs were investigated in mice. Mice were chronically treated with morphine (8-45 mg/kg, s.c.). Several withdrawal signs were observed following naloxone challenge in morphine-dependent mice which had been pretreated with vehicle. Treatment with DSP-4 before the naloxone challenge suppressed the expression of morphine withdrawal signs, including jumping and "wet dog" shakes. Similarly, pretreatment with the beta 1-antagonist atenolol significantly reduced the incidence of naloxone-precipitated jumping and "wet dog" shakes. However, pretreatment with the beta 2-antagonist ICI118,551 suppressed the expression of "wet dog" shakes, but not that of jumping. These findings suggest that the central noradrenergic system may mediate the expression of withdrawal signs. The blocking effects of beta-antagonists indicate that naloxone-precipitated jumping may be mediated predominantly by beta 1-adrenoceptors, while naloxone-precipitated "wet dog" shakes may be mediated by both beta 1- and beta 2-adrenoceptors.