Neuroleptic-like effects of gamma-hydroxybutyrate: interactions with haloperidol and dizocilpine

gamma-Hydroxybutyrate (GHB) is a drug of abuse with multiple mechanisms of action. Consistent with its ability to modulate dopaminergic systems, GHB reportedly shares behavioral effects with neuroleptics and interacts with them in a synergistic manner. Here, we examined the ability of GHB and haloperidol to induce catalepsy and to affect operant responding. When given alone, both compounds induced catalepsy and decreased response rate. When given together, however, they produced these effects in an additive manner. This is further evidence that GHB has neuroleptic-like effects, but suggests that GHB interacts additively, not synergistically, with neuroleptics. The mechanisms involved in GHB- and haloperidol-induced catalepsy are different because the N-methyl-D-aspartate (NMDA) receptor antagonist, dizocilpine (MK-801), attenuated the cataleptic effects of haloperidol, but enhanced those of GHB. The latter finding suggests that other NMDA receptor antagonists (e.g., the drugs of abuse--phencyclidine and ketamine) may also interact synergistically with GHB.