Drug Discrimination in Rats Under Concurrent Variable‐interval Variable‐interval Schedules

Abstract

Eight rats were trained to discriminate pentobarbital from saline under a concurrent variable-interval (VI) VI schedule, on which responses on the pentobarbital-biased lever after pentobarbital were reinforced under VI 20 s and responses on the saline-biased lever were reinforced under VI 80 s. After saline, the reinforcement contingencies programmed on the two levers were reversed. The rats made 62.3% of their responses on the pentobarbital-biased lever after pentobarbital and 72.2% on the saline-biased lever after saline, both of which are lower than predicted by the matching law. When the schedule was changed to concurrent VI 50 s VI 50 s for test sessions with saline and the training dose of pentobarbital, responding on the pentobarbital-biased lever after the training dose of pentobarbital and on the saline-biased lever after saline became nearly equal, even during the first 2 min of the session, suggesting that the presence or absence of the training drug was exerting minimal control over responding and making the determination of dose-effect relations of drugs difficult to interpret. When the pentobarbital dose-response curve was determined under the concurrent VI 50-s VI 50-s schedule, responding was fairly evenly distributed on both levers for most rats. Therefore, 6 additional rats were trained to respond under a concurrent VI 60-s VI 240-s schedule. Under this schedule, the rats made 62.6% of their responses on the pentobarbital-biased lever after pentobarbital and 73.5% of their responses on the saline-biased lever after saline, which also is lower than the percentages predicted by perfect matching. When the schedule was changed to a concurrent VI 150-s VI 150-s schedule for 5-min test sessions with additional drugs, the presence or absence of pentobarbital continued to control responding in most rats, and it was possible to generate graded dose-response curves for pentobarbital and other drugs using the data from these 5-min sessions. The dose-response curves generated under these conditions were similar to the dose-response curves generated using other reinforcement schedules and other species.

THE ROLE OF DOPAMINE IN REINFORCEMENT: CHANGES IN REINFORCEMENT SENSITIVITY INDUCED BY D1-TYPE, D2-TYPE, AND NONSELECTIVE DOPAMINE RECEPTOR AGONISTS

“…The b parameter represents bias, or the animal's tendency to choose one response manipulandum or reinforcer alternative over the other, independent of the reinforcement value of the two choices. Several studies have successfully used the matching paradigm to investigate sensitivity to reinforcement during drug exposure (e.g., Egli, Schaal, Thompson, & Clearly, 1992;Martinetti, Andrzejewski, Hineline, & Lewis, 2000), or when the reinforcer choice consisted of two pharmacological agents or a pharmacological agent and food (Anderson & Woolverton, 2000;Belke & Neubauer, 1997;McMillan & Hardwick, 2000;McMillan, Li, & Snodgrass, 1998;Woolverton & Alling, 1999). The model has great potential for examining the role of dopamine D 1 -like and D 2 -like receptors in choice responding and reward.…”

Drug Discrimination Under Two Concurrent Fixed‐interval Fixed‐interval Schedules

“…The data from the present experiments suggest that previous difficulties in studying drug discrimination in rats using concurrent reinforcement schedules (McMillan & Hardwick, 2000) may reflect a difference between rats and pigeons. In rats, a concurrent VI 40s VI 80-s schedule maintained strong control over responding, but the training drug provided only weak control over responding when the drug-substitution tests were conducted under a concurrent VI 50-s VI 50-s schedule.…”

“…These findings are consistent with data from simple FR and simple fixed-interval (FI) schedules (Massey, McMillan, & Wessinger, 1992), both FI and FR components of multiple schedules (Snodgrass & McMillan, 1991;McMillan & Hardwick, 1996), concurrent FR FR schedules (McMillan & Li, 1999a), concurrent FI FI schedules (McMillan, Li, & Hardwick, 1997), and concurrent variable-interval (VI) VI schedules (Snodgrass & Mc-Millan, 1996). Although most of these experiments were conducted using pigeons, some of these findings have been replicated with rats (McMillan & Hardwick, 2000). In most of the experiments, pentobarbital has served as the training drug, but these effects have been produced with other training drugs (Massey et al, 1992;McMillan, Cole-Fullenwider, Hardwick, & Wenger, 1982).…”

“…Pentobarbital was selected as the training drug for these experiments so that the results could be compared directly to our previous experiments in which pentobarbital was established as the discriminative stimulus under concurrent schedules (McMillan & Hardwick, 2000;McMillan & Li, 1999b;McMillan et al, 1997;Snodgrass & McMillan, 1996). Chlordiazepoxide and ethanol were substituted for pentobarbital in generalization tests because these drugs have been reported to substitute as discriminative stimuli for pentobarbital in drug-discrimination studies (Colpaert, Desmedt, & Janssen, 1976).…”

Navigation in the Morris Swim Task as a Baseline for Drug Discrimination: A Demonstration With Morphine

“…It is important to note that these graded functions were not simply the result of averaging across subjects or averaging across dose determinations within subjects (see Figure 3). Thus, it is possible that the present procedure may offer a general method by which graded drugdiscrimination functions may be obtained within subjects (see also McMillan & Hardwick, 2000;Snodgrass & McMillan, 1996).…”