ArticlesInitial Characterization of PMMA as a Discriminative Stimulus1
Section snippets
Methods
The subjects were six male Sprague-Dawley rats (Charles River Laboratories) weighing 250–300 g at the beginning of the study. The animals were first trained to lever-press for sweetened milk reward using standard two-lever operant chambers (Coulbourn Instruments, Lehigh Valley, PA, model E10-10) housed within sound- and light-attenuating outer chambers. Once lever-pressing behavior was acquired, the animals were trained to discriminate intraperitoneal (IP) injections of PMMA (1.25 mg/kg) from
Results
Six rats were trained to discriminate 1.25 mg/kg of PMMA from saline vehicle. Administration of PMMA doses lower than the training dose resulted in decreased responding on the PMMA-appropriate lever; response rates were not significantly different (see Table 2) following the different doses of PMMA or 1 ml/kg of saline. The ED50 dose for PMMA was calculated to be 0.44 mg/kg. The PMMA stimulus failed to generalize to either (+)amphetamine or DOM. In both instances, 1 mg/kg of drug produced
Discriminative Stimulus Profile
PMMA is a structurally simple, yet pharmacologically interesting molecule. Although it bears significant structural similarity to other phenylisopropylamine stimulants, and although it would be anticipated on the basis of established structure-activity relationships [23] to be a central stimulant, early studies failed to demonstrate any quantifiable amphetamine-like stimulant character for this agent [13]. Likewise, PMMA was shown to be pharmacologically distinct from the phenylisopropylamine
Summary
In conclusion, then, we have demonstrated that PMMA serves as a training drug in rats, that the stimulus properties of PMMA are dose-dependent, and that its stimulus generalization profile is more similar to that of MDMA than to those of (+)amphetamine or DOM. Lacking stimulant or hallucinogen-like stimulus qualities, PMMA may be considered to be qualitatively similar to MBDB. However, being structurally simpler than either MDMA or MBDB, and being several times more potent than MDMA as a
Acknowledgements
This work was supported, in part, by US PHS grant DA 01642.
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