MDMA (Ecstasy) substitutes for the ethanol discriminative cue in HAD but not LAD rats.
4-methylenedioxyamphetamine/*pharmacology; Alcohol Drinking/*genetics/psychology; Animals; Central Nervous System Depressants/*pharmacology; Cues; Discrimination (Psychology)/*drug effects; Discrimination Learning/drug effects; Dose-Response Relationship; Drug; Ethanol/*pharmacology; Generalization; Male; N-Methyl-3; Piperazines/pharmacology; Rats; Serotonin Agents/*pharmacology; Serotonin Receptor Agonists/pharmacology; Stimulus
Selectively bred high- and low-alcohol-drinking (HAD/LAD) rats were trained to discriminate the interoceptive stimuli produced by IP-administered 600 mg/kg ethanol (10% w/v in a two-lever, food-motivated operant task. Once criterion discrimination was attained, animals were tested with 3.0, 1.5, 1.0, and 0.5 mg/kg MDMA. Although no differences in alcohol discrimination were observed between the HAD and LAD animals, the HAD line was significantly more sensitive than the LAD line to the effects of MDMA. These results provide additional information to the growing body of evidence suggesting serotonergic mediation of some of the behavioral effects of ethanol.
Meehan S M; Gordon T L; Schechter M D
Alcohol (Fayetteville, N.Y.)
1995
1995-12
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1016/0741-8329(95)02004-7" target="_blank" rel="noreferrer noopener">10.1016/0741-8329(95)02004-7</a>
Drug-drug discrimination: stimulus properties of drugs of abuse upon a serotonergic-dopaminergic continuum.
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
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
Pharmacology, biochemistry, and behavior
1997
1997-01
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1016/S0091-3057(96)00161-X" target="_blank" rel="noreferrer noopener">10.1016/S0091-3057(96)00161-X</a>
Serotonergic-dopaminergic mediation of 3,4-methylenedioxymethamphetamine (MDMA, "ecstasy").
Male; Time Factors; Animals; Rats; Dopamine Agents/*pharmacology; Discrimination (Psychology)/*drug effects; Serotonin/*physiology; *Dopamine Antagonists; Serotonin Antagonists/*pharmacology; Amphetamines/*pharmacology; Dose-Response Relationship; Drug; Inbred Strains; 3; N-Methyl-3; Stimulus; 4-methylenedioxyamphetamine; 4-Methylenedioxyamphetamine/analogs & derivatives/*pharmacology; *Generalization
A series of three experiments were conducted to investigate the possible serotonergic and dopaminergic mediation of the discriminative stimulus properties of the "designer" drug MDMA. In Experiment 1, rats trained to discriminate 1.5 mg/kg (+/-)-MDMA from its vehicle at 20 min postadministration were shown to generalize to another drug of abuse, N-ethyl-3,4-methylenedioxyamphetamine (MDE) and to the serotonergically-active agents norfenfluramine and TFMPP. In contrast, testing of various dopaminergically-active agonists did not result in MDMA-like responding. In Experiment 2, dopaminergic and serotonergic antagonist were employed to observe their effect upon MDMA discrimination at 20 min postinjection. The serotonin antagonist pirenperone significantly decreased MDMA discrimination, whereas the dopamine decreasing drugs CGS 10746B and haloperidol had no effect. In Experiment 3, another group of rats were trained to discriminate MDMA at 105 min postadministration to investigate if, at this (later) time, the dopaminergic properties of MDMA may be more salient. Indeed, the dopaminergically-active drugs had a heightened effect upon MDMA at this later time, although the serotonergic component of the MDMA discriminative stimulus was predominant. The results suggest that the effects of MDMA at 20 min postadministration are solely serotonergic in nature. At 105 min postinjection there appears to be the presence of a weak dopaminergic component. This biphasic serotonergic-then-dopaminergic action of MDMA may explain the reported human experience with the drug, as well as the often controversial results in the literature.
Schechter M D
Pharmacology, biochemistry, and behavior
1988
1988-12
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1016/0091-3057(88)90390-5" target="_blank" rel="noreferrer noopener">10.1016/0091-3057(88)90390-5</a>