Mood-elevating effects of d-amphetamine and incentive salience: the effect of acute dopamine precursor depletion.
OBJECTIVE
Midbrain dopamine transmission is thought to regulate responses to rewarding drugs and drug-paired stimuli; however, the exact contribution, particularly in humans, remains unclear. In the present study, we tested whether decreasing dopamine synthesis, as produced by acute phenylalanine/tyrosine depletion (APTD), would alter responses to the stimulant drug, d-amphetamine.


METHODS
On 3 separate days, 14 healthy men received d-amphetamine (0.3 mg/kg, given orally) plus a nutritionally balanced amino acid mixture, the phenylalanine/tyrosine-deficient mixture or the phenylalanine/tyrosine-deficient mixture followed by the immediate dopamine precursor, L-DOPA (Sinemet, 2 x 100 mg/25 mg). Responses to these treatments were assessed with visual analog scales, the Profile of Mood States, and a computerized Go/No-Go task.


RESULTS
d-Amphetamine elicited its prototypical subjective effects, but these were not altered by APTD. In comparison, APTD significantly increased commission errors on the Go/No-Go task and did so uniquely in conditions where subjects were rewarded for making correct responses; this effect of APTD was prevented by L-DOPA.


CONCLUSIONS
Together these results support the hypothesis that, in healthy men, dopamine is not closely linked to euphorogenic effects of abused substances but does affect the salience of reward-related cues and the ability to respond to them preferentially.
Leyton
Marco
M
Department of Psychiatry, McGill University, Montréal, Que. marco.leyton@mcgill.ca
aan het Rot
Marije
M
Booij
Linda
L
Baker
Glen B
GB
Young
Simon N
SN
Benkelfat
Chawki
C
D000328:Adult; D000339:Affect / Q000187:drug effects*; D001288:Attention / Q000187:drug effects; D002230:Carbidopa / Q000494:pharmacology; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D003913:Dextroamphetamine / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism*; D004311:Double-Blind Method; D004338:Drug Combinations; D006801:Humans; D007980:Levodopa / Q000494:pharmacology; D008297:Male; D009042:Motivation; D009483:Neuropsychological Tests; D010147:Pain Measurement; D010649:Phenylalanine / Q000172:deficiency*; D011930:Reaction Time / Q000187:drug effects; D014443:Tyrosine / Q000172:deficiency*
D000697:Central Nervous System Stimulants; D004338:Drug Combinations; C009265:carbidopa, levodopa drug combination; D014443:Tyrosine; D007980:Levodopa; D010649:Phenylalanine; D002230:Carbidopa; D003913:Dextroamphetamine; D004298:Dopamine