Acute Phenylalanine/Tyrosine Depletion Reduces Motivation to Smoke Cigarettes Across Stages of Addiction

Abstract

The neurobiology of tobacco use is poorly understood, possibly in part because the relevant mechanisms might differ depending on past nicotine exposure and degree of addiction. In the present study we investigated whether these factors might affect the role of dopamine (DA). Using the acute phenylalanine/tyrosine depletion method (APTD), DA synthesis was transiently decreased in three groups of abstinent smokers (n=47): (1) early low-frequency smokers, who had smoked a maximum of five cigarettes per day for less than one year, (2) stable low-frequency smokers smoking at the same level as early low-frequency smokers for at least 3 years, and (3) stable high-frequency smokers, who smoked a minimum of 10 or more cigarettes per day for at least 5 years. Motivation to obtain tobacco was measured using a progressive ratio breakpoint schedule for nicotine-containing and de-nicotinized cigarettes. Compared with a nutritionally balanced control mixture, APTD decreased the self-administration of nicotine-containing cigarettes, and this occurred in all three groups of smokers. The results suggest that DA influenced the willingness to sustain effort for nicotine reward, and this was seen in participants at all three levels of cigarette addiction. In the transition from sporadic to addicted use, the role of DA in the motivation to seek drug may change less than previously proposed.

Dopamine and light: dissecting effects on mood and motivational states in women with subsyndromal seasonal affective disorder

“…49,50 The present study indicates that lowered DA can also reduce the motivation to work for a nonpharmacological reward. The measure of motivation was the PR breakpoint task.…”

Inflammation Effects on Motivation and Motor Activity: Role of Dopamine

“…In contrast, subtler augmentations of DA, such as L-3,4-dihydroxyphenylalanine (L-DOPA) administration, show no effect on hedonic response, despite clear modulation of motivation and response vigor (Beierholm et al, 2013;Liggins et al, 2012;Sharot et al, 2012;Sharot et al, 2009). Further, transient reduction of DA increased subjective reports of boredom and apathy, with no effect on affective ratings (McLean et al, 2004;Venugopalan et al, 2011).…”

“…Also in keeping with animal studies, effort expenditure for rewards can be increased or decreased through either potentiation (Wardle et al, 2011) or attenuation (Venugopalan et al, 2011) of DA levels, and individual differences in striatal DA release predict effort-related preferences (Treadway et al, 2012b).…”

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“…Administration of haloperidol and risperidone to normal human volunteers was shown to induce negative symptoms as measured by the Positive and Negative Symptoms Scale (Artaloytia et al, 2006). Furthermore, Venugopalan et al (2011) reported that catecholamine depletion reduced the tendency to work for cigarettes in smokers responding on a progressive ratio operant schedule.…”