Abstract
Because of the low discriminability of most neuroleptics, their use as stimuli in two-lever drug discrimination procedures has not been widespread. Several recent reports have demonstrated that the atypical neuroleptic clozapine (CLZ) has stronger cue properties than typical neuroleptics such as haloperidol (HAL). Most of these studies have tested animals trained to discriminate CLZ from vehicle. The present study examined the effects of CLZ, HAL, and three centrally acting serotonergic drugs (ritanserin, MDL 72222, and buspirone) in a drug-drug discrimination procedure with rats trained to discriminate CLZ (5.0 mg/kg) from HAL (0.03 mg/kg). Rats responded predominantly on the CLZ lever during substitution tests with CLZ. Substitution tests with the other four drugs produced 50% or less responding on the CLZ lever. These results are consistent with those of a previous study in which rats were trained to discriminate CLZ from vehicle (Wiley & Porter, 1992) and suggest that the CLZ cue is not mediated by blockade of dopamine D2 receptors, antagonism at 5-HT2 or 5-HT3 receptors, or agonistic activity at 5-HT1A receptors. Potential clinical implications of these results are discussed.
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The authors express appreciation to Robert Balster for his gift of MDL 72222 and to Daniel Kimbrough for his gift of ritanserin.
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Wiley, J.L., Porter, J.H. Effects of serotonergic drugs in rats trained to discriminate clozapine from haloperidol. Bull. Psychon. Soc. 31, 94–96 (1993). https://doi.org/10.3758/BF03334149
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DOI: https://doi.org/10.3758/BF03334149