Behavioural effects of glutamate receptor agonists in morphine-dependent rats

Glutamate receptors are implicated in the development and expression of dru g dependence. Substantial experimental evidence suggests that antagonists a cting at the N-methyl-D-aspartate (NMDA) subtype of glutamate receptors att enuate the severity of opioid withdrawal. However, it is less clear whether opioid withdrawal can be potentiated by agonists of glutamate receptors. T he present study evaluated the behavioural effects of various agonists of g lutamate receptors, as well as a nitric oxide (NO) donor, in morphine depen dent rats trained to discriminate 0.1 mg/kg of naloxone from saline. None o f the following drugs produced appreciable levels of naloxone-like respondi ng (substitution tests) or potentiated the discriminative stimulus effects of naloxone: NMDA (3-56 mg/kg), glycine (100-1000 mg/kg), glutamate (1000-3 000 mg/kg), kainate (0.53 mg/kg), isosorbide dinitrate (30-300 mg/kg). Neve rtheless, expression of some morphine withdrawal-like somatic and behaviour al signs ('wet-dog'-like shaking, scream on touch, ptosis, tremor, chewing, weight loss) was facilitated by NMDA glycine, and isosorbide dinitrate. Th ese results suggest that, compared to somatic symptoms, subjective effects of opioid withdrawal (as reflected by discriminative stimulus effects) are not mimicked by direct activation of glutamate receptors. (C) 1999 Lippinco tt Williams & Wilkins.