Practice-augmented tolerance to triazolam: evidence from an analysis of operant response durations and interresponse...

In order to investigate contingent tolerance to triazolam (TZ), 16 rats were trained with a water reinforcer to respond under a multiple fixed ratio 30 (FR 30)-differential reinforcement of low rate 20-s (DRL 20) schedule, during daily 20-min sessions. FR 30 and DRL 20 performances were assessed with measures of response rate, response duration, interresponse times, and reinforcers delivered. In addition, operant responses for each schedule component were divided into fast and slow subclasses, based on interresponse times less than 1s and greater than 1s. Initial dose-effect functions for these behavioural measures were obtained for TZ (0.05-0.5mg/kg). After a 30-day chronic TZ (0.5mg/kg) exposure period, during which half of the rats were gavaged pre-session (PRE) and the other half were gavaged post-session (POST), dose-effect functions were redetermined with a wider dose range (0.05-3.0mg/kg). The redetermined dose-effect functions for FR rate indicated that both PRE and POST groups developed resistance to the rate-suppressing effects of TZ. In addition, the PRE group displayed more tolerance than the POST group on some, but not all, measures, especially at doses higher than 0.5mg/kg. The greater tolerance in the PRE group was observed for number of reinforcers in the DRL 20 component, for response duration for the slow subclass of responses in both FR 30 and DRL 20 components, and for the fast subclass of responses in the DRL 20 component. Moreover, in the PRE group, tolerance occurred to the response duration measure even though the chronic dose of 0.5mg/kg had little effect on this measure. These results demonstrate the value of microanalytic methods in addressing the problem of contingent tolerance. In addition, the data suggest that extensive experience of response execution under the influence of a drug can have an "inoculating effect" against the higher doses of the drug even in the absence of large disruptions in behaviour during the drugged practice itself.