Modulating tobacco smoking rates by dopaminergic stimulation and blockade

Abstract

This study was designed to demonstrate that dopaminergic stimulation would result in decreased smoking behavior and nicotine intake, whereas dopaminergic blockade would result in increased smoking behavior and nicotine intake, in the same subjects. In prior human studies, a dopaminergic antagonist, haloperidol, increased smoking and/or nicotine intake, and a dopamine agonist, bromocriptine, decreased smoking. The smoking behavior of 20 heavy smokers was observed on two separate visits in a randomized, double-blind, repeated-measures-within-subject design. In the drug-reversal design, either bromocriptine (2.5 mg) or haloperidol (2.0 mg) was administered at each 5-h session, during which subjects smoked their own cigarettes ad libitum. Smoking topography was measured using a thermistor flow detector apparatus. Subjects smoked their cigarettes faster (p<0.05) and total puffing time was greater (p<0.05) with haloperidol than with bromocriptine. There was a trend for both a shorter latency to smoke (p<0.10, one-tailed) during time of expected peak drug concentration and for a shorter inter-cigarette interval with haloperidol than with bromocriptine (p<0.10, one-tailed). Shiffman-Jarvik Withdrawal Scale craving subscale scores increased significantly more with haloperidol than with bromocriptine (p<0.05). Mean Profile of Mood States (POMS) scores differed significantly for only one subscale (Confusion: bromocriptine>haloperidol; p<0.05). These data support the hypothesis that nicotine mediates reinforcement from smoking via dopamine, and that smoking behavior can be manipulated within the same subjects in opposite directions by alternately stimulating and blocking dopamine.

Dopamine Signaling through D1-Like versus D2-Like Receptors in the Nucleus Accumbens Core versus Shell Differentially Modulates Nicotine Reward Sensitivity

“…Considerable evidence suggests that blockade of DAergic neurotransmission may potentiate the motivational properties of nicotine in human subjects. For example, neuroleptic blockade of DA transmission strongly increases smoking rates in human smokers (McEvoy et al, 1995;Caskey et al, 1999Caskey et al, , 2002. Furthermore, decreased levels of striatal DA receptors have been correlated with increased psychostimulant drug taking and craving in humans for cocaine (Volkow et al, 2001), heroin , amphetamine (Volkow et al, 2001), and nicotine (Dagher et al, 2001), all suggesting that disturbances in striatal DAergic transmission may increase vulnerability to the addictive properties of these drugs.…”

Selective Antagonism at Dopamine D3 Receptors Prevents Nicotine-Triggered Relapse to Nicotine-Seeking Behavior

“…In addition, haloperidol reduces the number of both nicotine containing and denicotinized cigarettes, thus suggesting the involvement of non-nicotinic mechanisms (Brauer et al, 2001). However, haloperidol has also been shown to increase smoking behavior in both schizophrenic patients (McEvoy et al, 1995) and nonpsychiatric subjects (Caskey et al, 1999(Caskey et al, , 2002Dawe et al, 1995). Interestingly, DA agonist treatment can reduce responding for nicotine self-administration.…”

Other Pharmacological and Developing Treatments in Smoking Cessation/Nicotine Vaccines

“…Bromokriptin: Bir çalışmada dopaminerjik agonist olan bromokrtiptinin sigara içme isteğini azalttığı gösterilmiş (30) . Başka bir çalışmada ise dopamin antagonisti olan halloperidolün bromokriptine göre sigara içme isteğini arttırdığı gösterilmiş olup yazarlar bu ilaçlarla sigara içme davranışının düzenlenebileceği sonucuna varmışlar (31) . Bu sonuçlar, dopamin reseptörleri üzerinden etkili olabilecek ilaçlar ile ilgili çalış-maların devamının gerekli olduğunu göstermektedir.…”