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Increasing the Selectivity of Drug Discrimination Procedures

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Abstract

In an attempt to increase the selectivity of drug discrimination, rats were trained to discriminate LSD (0.08 mg/kg) from a group of “other” compounds consisting of cocaine (10 mg/kg), pentobarbital (5 mg/kg), and saline. Acquisition of this LSD-other discrimination was rapid (31 days) in chambers equipped with retractable levers and did not differ significantly from that of a group of animals trained to discriminate LSD from saline (26 days). In substitution (generalization) tests, hallucinogens such as LSD, DMT, and DOM mimicked LSD in a dose-dependent manner in both groups. The designer drug (±)MDMA substituted for LSD in the LSD-other group (ED50 = 1.38) but did not substitute for the training drug in the LSD-ND group; neither (+) MDMA nor PCP mimicked LSD in either group. Most importantly, lisuride, quipazine, and yohimbine, drugs that have been described as “false positives,” substituted for LSD in animals trained to discriminate LSD from saline (ED50s = 0.012, 1.662, 2.344, respectively), but not in animals trained to discriminate LSD from other drugs. Thus, the LSD-other training procedure can be described as more selective than the standard drug-ND procedure.

Section snippets

Subjects

Experimentally naive male, Sprague–Dawley rats (n = 22), 60 days old at the beginning of experimentation, were purchased from Charles River Breeding Laboratories, Wilmington, MA. They were housed individually in a colony maintained on a 12 L:12D schedule, with lights on from 0700–1900 h. Temperature and relative humidity were held constant at 20–22°C and 40–50%, respectively. Initially, animals had free access to both food and water. Five days before training, access to water was restricted for

Results

The acquisition of the LSD-saline and LSD-other discriminations are shown in Fig. 1. Criterion was attained rapidly in both groups of animals, 24 sessions in the LSD-saline group (top), and 31 sessions in the LSD-other group (bottom), and did not differ significantly as a function of training condition, t(20) = 1.22, p = 0.2. In addition, rates of responding were relatively high, at least when compared with those reported previously in this laboratory (7). The average rate for each animal in

Discussion

The results of this experiment indicate that rats can be trained to discriminate LSD from a group of “other” drugs consisting of a CNS depressant, pentobarbital, a CNS stimulant, cocaine, and saline. Thus, they confirm and extend the work of Overton (15) to a different class of compounds (hallucinogens rather than depressants). Thus far, however, the limits of the LSD discrimination have not been explored by varying either drugs or doses in the “other” group. This task should be undertaken

Acknowledgements

This work was supported by USPHS Research Grant DA02543 from the National Institute on Drug Abuse.

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Present address: Department of Public Health, University of South Carolina, Columbia, SC 29208.

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