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Dopaminergic mediation of the discriminative stimulus functions of modafinil in rats
- Source :
- Psychopharmacology. 232:4411-4419
- Publication Year :
- 2015
- Publisher :
- Springer Science and Business Media LLC, 2015.
-
Abstract
- Modafinil is a wake-promoting drug with FDA approval for the treatment of excessive daytime sleepiness that has been prescribed for ADHD and recently assessed as a potential treatment for psychostimulant dependence. Previous research indicates that modafinil modestly increases locomotor activity and produces similar discriminative stimulus effects to psychostimulants in rodents, although the subjective effects of modafinil are reportedly distinct from those of cocaine or amphetamine in humans with a history of psychostimulant abuse.The current study employed drug discrimination procedures in rats to examine the pharmacological actions contributing to modafinil's discriminative stimulus functions.Eight male Sprague-Dawley rats were trained to discriminate intragastric administration of 256 mg/kg modafinil from vehicle (5% arabic gum) under a FR 20 schedule of food reinforcement. Substitution tests were conducted with various dopaminergic agents (d-amphetamine, cocaine, PNU-91356A, GBR 12909, methylphenidate) and nondopaminergic agents (nicotine, ethanol). Antagonist tests were conducted with the selective D1 antagonist, SCH 39166, and the nonselective D2 antagonist, haloperidol.Rats trained to discriminate modafinil displayed complete stimulus generalization to cocaine, methylphenidate, and GBR 12909 and the discrimination was completely blocked by both SCH 39166 and haloperidol. Evidence for significant partial substitution was obtained with d-amphetamine, PNU-91356A, and nicotine.Results strongly support the role of dopaminergic mechanisms in the discriminative stimulus functions of modafinil, although further evaluation regarding the contribution of other neurotransmitter systems to these effects should be continued. The findings are discussed in light of clinical research efforts with modafinil as a treatment for psychostimulant dependence.
- Subjects :
- Male
Nicotine
Dextroamphetamine
Dopamine
Dopamine Agents
Excessive daytime sleepiness
Modafinil
Pharmacology
Generalization, Psychological
Piperazines
Rats, Sprague-Dawley
Wakefulness-Promoting Agents
Cocaine
mental disorders
Animals
Medicine
Benzhydryl Compounds
Amphetamine
business.industry
Methylphenidate
Dopaminergic
Rats
Central Nervous System Stimulants
medicine.symptom
business
Stimulus control
Reinforcement, Psychology
medicine.drug
Subjects
Details
- ISSN :
- 14322072 and 00333158
- Volume :
- 232
- Database :
- OpenAIRE
- Journal :
- Psychopharmacology
- Accession number :
- edsair.doi.dedup.....b79ab2d14a21214afc1ae31d0b4b57e4