Fluoxetine-induced attenuation of amphetamine self-administration in rats.
Daily injections of fluoxetine (5.0 mg/kg i.p.) to rats trained to self-administer intravenous d-amphetamine produced marked decreases in drug intake on three successive days of treatment. After fluoxetine injections were stopped, the number of daily amphetamine self-injections was still significantly reduced for an additional 2 days. When trained amphetamine self-administration animals were placed in an apparatus which delivered i.v. saline with each lever press, increased self-injection is observed. Acute fluoxetine injection did not alter this response. However, if fluoxetine is given prior to amphetamine exposure for 1 day and animals are then tested for the saline response, lever pressing activity is significantly reduced. These data might suggest that 5-hydroxytryptaminergic neurons mediate some aversive or negative reinforcing property of amphetamine. If true, this finding could be exploited clinically in cases of human psychomotor stimulant addiction.
D000662:Amphetamines; D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects*; D005473:Fluoxetine / Q000494:pharmacology*; D008297:Male; D009474:Neurons / Q000378:metabolism; D011437:Propylamines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011985:Receptors, Serotonin / Q000187:drug effects; D012701:Serotonin / Q000378:metabolism*; D019966:Substance-Related Disorders / Q000378:metabolism*
D000662:Amphetamines; D011437:Propylamines; D011985:Receptors, Serotonin; D005473:Fluoxetine; D012701:Serotonin