The behavioral pharmacological profile of a drug in a pertinent species is necessary to evaluate quantitatively how the drug functions as a reinforcer. Ongoing studies on the direct behavioral effects of drugs include a number of different paradigms. The study of the stimulus effects of a drug most often involves training animals with a drug as a discriminative stimulus. One project involves the assessment of both the acute and chronic effects of a variety of drugs on these discriminative stimulus functions. We have shown that a combination of fenfluramine (FEN) and phentermine (PHEN), which has previously been reported to be useful in the treatment of alcohol and cocaine addictions, can serve as a discriminative stimulus. Each of the separate components of the mixture was found to contribute equally toward the cue in an additive manner, without showing similarities to other abused substances (e.g. alcohol, cocaine, etc). In vivo microdialysis experiments confirmed the nature of interaction; FEN and PHEN selectively increased serotonin and dopamine respectively, while the mixture increased both amines by similar levels. Therefore the dual stimulation of the amines by the mixture may be the basis for the cueing effects of the drug mixture. Locomotor activity is also used to assess the behavioral effects of drug treatment. Chronic administration of cocaine has been shown to produce long-lasting and progressive enhancements in their locomotor effects. It has been suggested that understanding of the neurobiological mechanisms of this sensitization may provide insight into the neural substrates mediated drug-induced psychosis. We recently reported that repeated once daily intravenous injections of cocaine produces locomotor sensitization. Dopamine D1 and D2 dopamine receptor antagonists are more potent in blocking cocaine's locomotor effects in cocaine-naive animals than in cocaine-sensitized animals. While a withdrawal effect is often times hard to observe following treatment with psychomotor stimulants, we have recently observed a withdrawal effect following chronic amphetamine treatment on locomotor activity. Rats treated for 2 weeks with amphetamine show a disruption in stereotypy 24-48 hours following the cessation of treatment. This disruption is correlated with a number of changes in brain transcription factors, suggesting neural correlates to the observed behavioral effect can be determined
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