Influence of reinforcer type and route of administration on gamma-hydroxybutyrate discrimination in rats

Rationale. Possible effects of reinforcer type on the results of drug discrimination studies have not been examined systematically, but different deprivation operations and differentially effective reinforcers might well influence outcomes. Objective. Therefore, this study examined the influence of reinforcer (food or water) as well as route of administration (IP or IG) on gamma-hydroxybutyrate (GHB) discrimination. Methods. Four separate groups of six rats were trained under a resetting fixed-ratio schedule to discriminate between 300 mg/kg GHB and vehicle under these conditions, then generalization tests were conducted with gamma-butyrolactone (GBL), 1,4-butanediol (1,4-BD), ethanol, and ethanol plus 150 mg/kg GHB. Results. Food maintained significantly higher response rates than water, but there were no significant differences among the four training groups in response accuracy or sessions required to meet the discrimination criterion. Training conditions significantly affected the results of stimulus generalization tests. The IG-Water group was most sensitive to a lower dose of GHB, and only the IP-Water group failed to generalize to orally-administered GHB. Gamma-butyrolactone and 1,4-butanediol fully substituted in all except the IP-Food group. Ethanol did not fully substitute for GHB in any group, and the combination of GHB (150 mg/kg) and ethanol did not have additive effects. Conclusions. These results demonstrate that methodological variables during drug discrimination training can certainly influence the results of stimulus generalization. Future investigations into the behavioral and/or physiological mechanisms that account for these effects are warranted.