Drug-drug discrimination: stimulus properties of drugs of abuse upon a serotonergic-dopaminergic continuum.
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.
Schechter
M D
MD
Department of Pharmacology, Northeastern Ohio Universities College of Medicine, Rootstown 44272, USA.
D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D004192:Discrimination, Psychological / Q000187:drug effects*; D004298:Dopamine / Q000502:physiology*; D018491:Dopamine Agonists / Q000494:pharmacology; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005795:Generalization, Stimulus; D008238:Lysergic Acid Diethylamide / Q000494:pharmacology; D008297:Male; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000494:pharmacology; D009642:Norfenfluramine / Q000494:pharmacology; D011427:Propiophenones / Q000494:pharmacology; D051381:Rats; D012701:Serotonin / Q000502:physiology*; D018490:Serotonin Agents / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology; D019966:Substance-Related Disorders / Q000523:psychology*; D013764:Tetrahydronaphthalenes / Q000494:pharmacology; D013997:Time Factors
D000661:Amphetamine; D004298:Dopamine; D018491:Dopamine Agonists; D018765:Dopamine Uptake Inhibitors; D008238:Lysergic Acid Diethylamide; D018817:N-Methyl-3,4-methylenedioxyamphetamine; D009642:Norfenfluramine; D011427:Propiophenones; D012701:Serotonin; D018490:Serotonin Agents; D017366:Serotonin Receptor Agonists; D017367:Selective Serotonin Reuptake Inhibitors; D013764:Tetrahydronaphthalenes; C047806:monomethylpropion; C031349:7-hydroxy-2-N,N-dipropylaminotetralin