Drug-drug discrimination: stimulus properties of drugs of abuse upon a serotonergic-dopaminergic continuum.

Drug-drug discrimination: stimulus properties of drugs of abuse upon a serotonergic-dopaminergic continuum.

Schechter M D

Pharmacology, biochemistry, and behavior

1997

1997-01

Ten male N/Nih rats were trained to discriminate between the interoceptive cues produced by the purportedly dopaminergically-mediated drug d-amphetamine at 0.4 mg/kg intraperitoneally administered 20 min prior to training and those produced by the purportedly serotonergically-active agent norfenfluramine at 0.7 mg/kg. Once this discrimination was successfully acquired, the rats were tested with saline and with both drugs administered simultaneously and these manipulations were seen to produce random responding; indicating roughly equivalent cueing strength. Subsequently, various drugs thought to act upon serotonergic neurons, i.e., LSD and MDMA, were tested and shown to generalize in a dose-responsive manner to the norfenfluramine-appropriate lever. In contrast, the dopaminergically-active agent methcathinone and the D3 agonist 7-OH-DPAT produced generalization on the amphetamine-appropriate lever. Results are discussed in light of the increased specificity of behavioral testing available in a drug vs. drug discriminative paradigm using two drugs with different mechanisms of action.

4-methylenedioxyamphetamine/pharmacology; Amphetamine/pharmacology; Animals; Discrimination (Psychology)/*drug effects; Dopamine Agonists/pharmacology; Dopamine Uptake Inhibitors/pharmacology; Dopamine/*physiology; Dose-Response Relationship; Drug; Generalization; Lysergic Acid Diethylamide/pharmacology; Male; N-Methyl-3; Norfenfluramine/pharmacology; Propiophenones/pharmacology; Rats; Serotonin Agents/pharmacology; Serotonin Receptor Agonists/pharmacology; Serotonin Uptake Inhibitors/pharmacology; Serotonin/*physiology; Stimulus; Substance-Related Disorders/*psychology; Tetrahydronaphthalenes/pharmacology; Time Factors

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