Gamma-butyrolactone's discriminability and effect on low rates of lever pressing by rats: alone and in combination with D-amphetamine and naloxone.

Three studies examined gamma-butyrolactone (Gbl) for benzodiazepine-like effects on low rates of food reinforced lever pressing by rats. A fourth study established Gbl's discriminative properties. Additionally, d-amphetamine or naloxone was administered with Gbl to test hypotheses of Gbl's neurochemical mechanisms of action. In Experiment 1, Gbl caused a dose-related decrease in lever pressing during a fixed-interval reinforcement schedule. Contrary to previous reports, neither d-amphetamine nor naloxone reversed the depressive effects of a high dose of Gbl on behavior. In Experiment 2, Gbl increased lever pressing which had been suppressed in the presence of a tone correlated with response-independent foot-shock (conditioned suppression). These results are consistent with, and extend, previous findings of benzodiazepine-like antipunishment effects of Gbl. However, in Experiment 3, when brief electric shocks were presented after each lever press, Gbl did not increase lever pressing. These results show the limited generality of Gbl's antipunishment effect compared to broad spectrum anxiolytics. Experiment 4, a drug discrimination study, showed rats readily discriminated 150 and 125 mg/kg Gbl from saline. However, neither d-amphetamine nor naloxone generalized to the Gbl lever. Amphetamine partially blocked the discriminative properties of 150 mg/kg Gbl, whereas naloxone had little effect on Gbl's discriminative properties. Thus, there is some support for a direct catecholaminergic role in Gbl-related seizures and little support for opioid receptor participation. The results of Experiments 1 and 4 indicate that Gbl's effects on behavior are complex, and are not accounted for by hypotheses involving only catecholamine and/or opioid mechanisms of action.