Influence of acute or repeated restraint stress on morphine-induced locomotion: involvement of dopamine, opioid and glutamate receptors.

The development of restraint stress-induced sensitization to the locomotor stimulating effect of morphine (2 mg/kg i.p.) was investigated. In experiment 1, both a single restraint session (2 h) and a repeated restraint stress (2 h per day for 7 days), similarly enhanced the effects of morphine on motor activity. In experiment 2, we observed that this sensitization was prevented by administration of both D(1) and D(2) dopaminergic antagonist [SCH-23390 (0.5 mg/kg i.p.) and (+/-)-sulpiride (60 mg/kg i.p.)] 10 min prior to the stress session. In experiment 3, we showed that an opioid antagonist pretreatment [naltrexone (1 mg/kg i.p.) 10 min prior to stress session, suppressed the stress-induced sensitization after morphine administration. In experiment 4, pretreatment with a non-competitive antagonist of the N-methyl-D-aspartate (NMDA) type of glutamate receptors [(+)-MK-801 (0.1 mg/kg i.p.)], 30 min prior to the acute restraint session, prevented the development of sensitization to morphine. All these results suggest that: (1) sensitization to morphine on stimulating locomotor effect does not depend on the length of exposure to stress (acute vs. repeated); (2) stimulation of both D(1) and D(2) dopaminergic receptors is necessary for the development of restraint stress-induced sensitization to morphine; (3) an opioid system is also involved in this sensitization process; and (4) the stimulation of glutamatergic NMDA receptors is involved in this acute restraint-induced effect. Copyright 2002 Elsevier Science B.V.