MODIFICATION OF NALOXONE-PRECIPITATED WITHDRAWAL SYMPTOMS IN MICE BY DRUGS ACTING ON ALPHA(2)-ADRENOCEPTORS

Modification of naloxone-precipitated withdrawal symptoms by drugs act ing on alpha-adrenoceptors was investigated in morphine-dependent mice . Clonidine (0.05-1 mg/kg) attenuated most withdrawal symptoms, but po tentiated withdrawal hypothermia. jumping was attenuated by doses of c lonidine up to 0.3 mg/kg, but markedly potentiated by 1 mg/kg. Prazosi n (0.05 mg/kg) neither had effects of its own, nor influenced those of clonidine. Both yohimbine (0.5-5 mg/kg) and idazoxan (1-10 mg/kg) pot entiated naloxone-precipitated withdrawal symptoms. When tested agains t a low dose of clonidine (0.2 mg/kg), idazoxan dose-dependently reduc ed the suppressive effects of clonidine on jumping, ''wet dog'' shakes , burrowing and bodyweight loss but potentiated the hypothermic respon se of clonidine. Yohimbine similarly reduced the suppressive effect of clonidine on body-weight loss and potentiated its hypothermic respons e, but unlike idazoxan, it did not influence the inhibition by clonidi ne of ''wet dog'' shakes, and markedly reversed tie suppression of jum ping and burrowing into potentiation. Yohimbine and idazoxan also diff ered with respect to their antagonistic profile against a high dose of clonidine (1 mg/kg). Yohimbine further aggravated the potentiation of jumping by clonidine, reduced the effect on body-weight loss and reve rsed the suppression of burrowing by clonidine. On the other hand, ida zoxan markedly reduced the potentiation of jumping by clonidine, and r eversed its effect on ''wet dog'' shakes and burrowing. These findings indicate that clonidine has a biphasic effect on jumping, and disclos e differences in the antagonistic profiles between yohimbine and idazo xan. The results suggest that in addition to alpha(2)-adrenoceptors, n on-adrenergic imidazoline receptors sensitive to clonidine and idazoxa n but not to yohimbine may modulate the expression of morphine withdra wal symptoms.