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.