POSSIBLE INVOLVEMENT OF NMDA RECEPTOR-MEDIATED TRANSMISSION IN BARBITURATE PHYSICAL-DEPENDENCE

1 The competitive antagonists at the N-methyl-D-aspartate (NMDA) recep tor,CGP39551 and CGP37849, protected against the barbiturate withdrawa l syndrome in mice, as measured by ratings of convulsive behaviour on handling. 2 The effective doses of these compounds were lower than tho se required to prevent seizures due to NMDA in naive animals; these we re in turn lower than those needed to prevent the convulsive effects o f the alpha-aminobutyric acid (GABA) antagonist, bicuculline. 3 The NM DA-receptor antagonists did not alter the increase in the incidence of convulsions due to the GABAA antagonist, bicuculline, that is seen du ring barbiturate withdrawal, although the latencies to these convulsio ns during barbital withdrawal were significantly increased after CGP39 551. 4 Barbiturate withdrawal did not affect the convulsive actions of NMDA, whether measured by the incidence of convulsions or by intraven ous infusion. 5 The B-max for [H-3]-dizocilpine ([H-3]-MK801) binding was significantly increased by chronic barbital treatment in cerebroco rtical but not in hippocampal tissues, while the K-d remained unaltere d in either case. 6 At 1 h and 24 h after; administration of a single dose of barbitone, the B-max for [H-3]-dizocilpine binding was unalter ed in cerebrocortical tissue. Acute addition of barbitone in vitro did not alter [H-3]-dizocilpine binding or the displacement of binding of thienylcyclohexylpyridine