Acute Phenylalanine Tyrosine Depletion Reduces Motivation to Smoke Cigarettes
The neurobiology of tobacco use at varying stages of addiction is not well understood. Studies in laboratory animals, however, implicate a role for nicotine-induced dopamine (DA) release. Following acute administration, nicotine binds to nicotinic cholinoceptors on DA cell bodies in the ventral tegmental area of the midbrain and elicits DA release in the ventral striatum. Repeated nicotine exposure can lead to progressive increases in its rewarding and behaviorally activating effects. For example, initial intermittent exposures to nicotine (three to six times) result in progressively greater effects on locomotor activity, enhance the acquisition of self-administration, increase conditioned place preferences, and precipitate greater DA overflow in the nucleus accumbens. Preventing this DA response disrupts nicotine self-administration and nicotine-related conditioned place preferences. The contribution of DA following more extensive nicotine exposure, though, remains largely unexplored.
Attempts to translate these findings to humans have been equivocal. Functional neuroimaging studies have demonstrated DA release in response to cigarette smoking, but attempts to alter smoking behavior by decreasing DA transmission have provided contradictory results. In these studies, smoking patterns were seen to increase, and remain unchanged. This variability might reflect differences in nicotine self-administration paradigms, the use of nonspecific DA receptor antagonists, or a change in the role of DA, as smokers transition from occasional to dependent cigarette use.
In the present study, researchers investigated the effect of decreasing DA transmission on the motivation to smoke and self-reports of cigarette pleasure and craving at three different stages of tobacco addiction:
(1) low-frequency early smokers (LFES), who have smoked less than 1 year and smoke no more than five cigarettes per day and not every day,
(2) low-frequency stable smokers (LFSS), who have smoked for at least 3 years, smoking no more than five cigarettes a day, not necessarily every day, and
(3) high frequency stable smokers (HFSS) who have smoked for more than 5 years and smoke 10 or more cigarettes per day, every day.
Motivation to obtain cigarettes was measured using a progressive ratio (PR) breakpoint paradigm adapted for humans. DA transmission was decreased using the acute phenylalanine/tyrosine depletion method (APTD).
The present study provides the first investigation of the role of DA in low-frequency smokers. As seen previously in non-dependent users of other substances, reducing DA transmission decreased self-administration behavior. More importantly, the same reduction was seen in high-frequency, nicotine-dependent smokers. Together, these findings suggest that DA affects motivation to obtain drug reward across degrees of addiction, at least in the case of tobacco.
Venugopalan VV, Casey KF, O'Hara C, et al. Acute Phenylalanine/Tyrosine Depletion Reduces Motivation to Smoke Cigarettes Across Stages of Addiction. Neuropsychopharmacology 2011;36(12):2469-76. Neuropsychopharmacology - Abstract of article: Acute Phenylalanine/Tyrosine Depletion Reduces Motivation to Smoke Cigarettes Across Stages of Addiction
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.
]
)]). So a nice load of horse shit IMO. And proof again of Big pharma's attempts to stamp out naturally grown drugs that can help treat conditions like mental illness They said in their that its BS that nicotine is good self medication for mentally ill. Right. You bet your ass it is... But no, buy our Seroquel and die of diabetes in 25 years instead.. LOL. Or buy or bupropion and have nervous ticks and parkinsons when your 60 instead. They are just pissed cause they cant create a drug half as addictive.... And I am sure some of the assholes writing these articles are just that. And crazy as shit from lack of nicotine.... LOL
