Cortical spreading depression blocks naloxone-induced escape behaviour in morphine pretreated mice

Mice treated with morphine (100 mg/kg SC) and 3 hr later with naloxone (30 mg/kg) developed an acute abstinence syndrome characterized by escape attempts (rearing, wall-climbing, jumping) and unconditioned motor (head-shaking, jerking) and visceral signs. Functional decortication by spreading depression (SD), elicited 15 min before naloxone injection by epidural application of 25% KCl, abolished the escape behaviour without interfering with other abstinence signs. Electrophysiological recording confirmed reliable generation of cortical SD waves under the conditions of the experiment. The SD effect indicates that the escape behaviour of morphine dependent mice is a conditioned compensatory response to the unconditioned effects of the drugs.