The interactions of&agr;2-adrenoceptors and acute restraint stress with morphine state-dependent memory of passive avoidance were examined in mice. Memory acquired following pre-training morphine administration (5 mg/kg, i.p.) was dose- and time-dependently retrieved by pre-test morphine; this effect was reversible by yohimbine (1 mg/kg). Pre-test clonidine (0.005–0.1 mg/kg) was also effective in restoring morphine-induced memory. Pre-training clonidine (2 mg/kg) induced an amnestic effect that was restorable by pre-test clonidine or morphine; this effect was also blocked by yohimbine. Acute pre-training stress for 2 h induced an amnestic effect that was reversible by pre-test morphine (1 and 5 mg/kg) or clonidine (0.01 and 0.1 mg/kg). Finally, acute pre-test stress could restore the impairment of memory induced by pre-training morphine. The data are suggestive of a functional interaction betweenμ-opioid,&agr;2-adrenergic receptors and stress in modulating state-dependent learning and memory.