Modafinil evokes striatal [(3)H]dopamine release and alters the subjective properties of stimulants
by
Dopheide MM, Morgan RE, Rodvelt KR,
Schachtman TR, Miller DK.
Department of Psychological Sciences,
University of Missouri,
Columbia MO, USA;
Department of Psychology,
Monmouth College,
Monmouth IL, USA.
Eur J Pharmacol. 2007 Apr 5;

ABSTRACT

Modafinil is a mild psychostimulant used for the treatment of sleep and arousal-related disorders, and has been considered a pharmacotherapy for cocaine and amphetamine dependence; however, modafinil's mechanism of action is largely unclear. The present study investigated modafinil using drug discrimination and slice superfusion techniques. Rats were trained to discriminate cocaine (1.6 or 5 mg/kg) or amphetamine (0.3 mg/kg) from saline injection for food reinforcement. Modafinil (64-128 mg/kg) substituted partially for both cocaine doses and amphetamine. Pretreatment with a lower modafinil dose (32 mg/kg) augmented the discriminative stimulus properties of cocaine (1.6 mg/kg dose group) and amphetamine. In neurochemical experiments, modafinil (100-300 muM) evoked [(3)H]overflow from rat striatal slices preloaded with [(3)H]dopamine in a concentration-dependent manner; however, modafinil was less potent and efficacious than amphetamine and nicotine. The dopamine transporter inhibitor nomifensine (10 muM) blocked modafinil-evoked [(3)H]overflow, and concentrations of modafinil (<100 muM) that did not have intrinsic activity attenuated amphetamine (1 and 3 muM)-evoked [(3)H]overflow. Modafinil-evoked [(3)H]overflow was not altered by the nicotinic acetylcholine receptor antagonist mecamylamine, and modafinil did not alter nicotine-evoked [(3)H]overflow, indicating that nicotinic acetylcholine receptors likely are not important for modafinil's mechanism of action. The present results indicate that modafinil evokes dopamine release from striatal neurons and is a psychostimulant that is pharmacologically similar to, but much less potent and efficacious than, amphetamine.

Dopamine
Narcolepsy
Modafinil: review
Modafinil: structure
Modafinil and serotonin
Modafinil and the marmoset
Excessive daytime sleepiness
Modafinil as an antidepressant
Modafinil versus amphetamine
Modafinil versus methylphenidate
Modafinil, amphetamine and sleep

Refs
and further reading

HOME
HedWeb
Nootropics
cocaine.wiki
Future Opioids
BLTC Research
MDMA/Ecstasy
Superhapiness?
Utopian Surgery?
The Abolitionist Project
The Hedonistic Imperative
The Reproductive Revolution
Critique of Huxley's Brave New World

The Good Drug Guide
The Responsible Parent's Guide
To Healthy Mood Boosters For All The Family