STUDY OF THE MECHANISMS INVOLVED IN BEHAVIORAL-CHANGES INDUCED BY FLUNITRAZEPAM IN MORPHINE-WITHDRAWAL

1. The attenuation of morphine withdrawal syndrome by acute benzodiaze pine administration has been well documented. However, the pharmacolog ical mechanisms implicated in this effect remain unclear. 2. In this s tudy, the possible participation of noradrenergic, serotonergic and be nzodiazepine receptors on flunitrazepam-modified morphine withdrawal s yndrome was investigated in mice. Flunitrazepam was associated to the noradrenergic antagonists prazosin (1 mg/kg) and propranolol (0.5 mg/k g), the serotonergic agents ritanserine (1 mg/kg) and p-chloro phenyla lanine (600 mg/kg), the benzodiazepine antagonist flumazenil(10 mg/kg) , and the benzodiazepine partial inverse agonist Ro 15-4513 (5 mg/kg). 3. The decrease in jumping behavior-induced by flunitrazepam was pote ntiated by prazosin, while ritanserine, flumazenil and Po 15-4513 bloc ked this effect. 4. Flunitrazepam-induced increase on wet dog shake fr equency was partially reduced by flumazenil, and strongly antagonized by ritanserine and Ro 15-4513. 5. Noradrenergic and serotonergic syste ms seem to be primarily implicated in the changes induced on jumping a nd wet dog shakes respectively. These modifications are induced throug h the activation of the benzodiazepine receptors.