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We investigated the impact of the administration of a tyrosine-depleting amino acid mixture compared to a balanced mixture on measures of mood, craving and selective processing of smoking-related cues in healthy cigarette smokers instructed to abstain from smoking for 12 h prior to, and during, the experiment. A modified stroop task was used to index selective processing of smoking-related cues. We observed evidence for an increase in subjective craving among males, and an attenuation of the selective processing of smoking-related cues compared to control cues among females, in the tyrosine-depleting condition compared to the balanced condition. No effects of mixture were observed on measures of subjective mood. These results tentatively support for the role of dopaminergic neurotransmission in mediating the response of cigarette smokers to smoking-related cues. In addition, these results also provide further evidence for sex differences in the factors that maintain cigarette smoking, in particular with respect to conditioned reinforcement of smoking behaviour, and suggest that the relationship between subjective craving and selective processing of smoking-related cues may differ in males and females.

The role of dopamine (DA) pathways in the pathophysiology of depressive disorder is poorly understood. However, because DA plays a key role in motivational behavior, it is important to study in a disorder characterized by anhedonia, lack of energy and psychomotor retardation. A recently developed dietary manipulation ('tyrosine (TYR) depletion') offers a novel method to assess the role of DA in major depression. We studied 15 euthymic women with a past history of recurrent depression, who received a 74 g amino-acid drink lacking TYR and phenylalanine (PHE) (TYR-free) and a balanced (BAL) amino acid drink on two separate occasions in a double-blind, random-order, crossover design. Plasma prolactin levels rose following the TYR-free drink relative to the balanced mixture, while performance on a spatial recognition memory task was impaired. However, relative to the BAL drink, the TYR-free drink did not lower objective or subjective measures of mood. We conclude that as in healthy volunteers, TYR depletion in euthymic subjects, with a past history of major depression, attenuated DA function, as reflected in increased plasma prolactin levels and decreased spatial memory performance. However ratings of depression were unaffected, suggesting that disruption of dopaminergic function by this manipulation does not induce a lowering of mood in individuals vulnerable to depression.