COMPETITIVE AND GLYCINE NMDA RECEPTOR ANTAGONISTS ATTENUATE WITHDRAWAL-INDUCED BEHAVIORS AND INCREASED HIPPOCAMPAL ACETYLCHOLINE EFFLUX IN MORPHINE-DEPENDENT RATS/

The present study has examined the glycine/N-methyl-D-aspartate (NMDA) receptor antagonist, R-(+)-3-amino-1-hydroxqpyrrolid-2-one (R-(+)-HA- 966) and the competitive NMDA receptor antagonist, cis-4-(phosphonomet hyl)piperidine-2-carboxyl acid (CGS 19755) on the behavioural syndrome and increased hippocampal acetylcholine efflux induced during morphin e-withdrawal in the rat. Subcutaneous naltrexone (1 mg/kg) injection, 48 hr after implantation of a 75 mg morphine pellet, induced a robust withdrawal syndrome consisting of wet dog shakes, ejaculations, mouth movements, ptosis, irritability to touch and diarrhoea. Pretreatment w ith the alpha(2)-adrenoceptor agonist, clonidine (0.1-0.4 mg/kg), R-()HA-966 (10-60 mg/kg) or CGS 19755 (5 or 10 mg/kg) significantly reduc ed the incidence of withdrawal behaviours. In addition, all three comp ounds significantly attenuated the increase in hippocampal acetylcholi ne efflux induced following naltrexone (1 mg/kg, s.c.) injection in mo rphine-dependent rats. These results provide further evidence demonstr ating that NMDA receptor antagonists attenuate both the behavioural an d neurochemical effects observed during morphine withdrawal in the rat . (C) 1997 Elsevier Science Ltd.