Abstract
Trace amine-associated receptor 1 (TAAR1) has emerged as a promising target for addiction treatments because it affects dopamine transmission in the mesolimbic pathway. TAAR1 is involved in the effects of addictive drugs, such as amphetamines, cocaine and ethanol, but the impact of TAAR1 on the effects of nicotine, the psychoactive drug responsible for the development and maintenance of tobacco smoking, has not yet been studied. This study was performed to investigate the possible modulatory action of TAAR1 on the effects of nicotine on locomotor behaviors in rats and mice. Pretreatment with the TAAR1 agonist RO5263397 dose-dependently decreased nicotine-induced hyperlocomotion in rats habituated to locomotor boxes, prevented the development of nicotine sensitization and blocked hypermotility in nicotine-sensitized rats at the highest tested dose (10 mg/kg). The lack of TAAR1 failed to affect the effects of nicotine on the locomotion of mutant mice. Based on the results of the present study, TAAR1 activation attenuates the locomotion-stimulating effects of nicotine on rats. These results further support the previously proposed hypothesis that TAAR1 is a promising target for the prevention and treatment of drug addiction. Further studies aimed at analyzing the effects of TAAR1 agonists on animal models of nicotine addiction are warranted.
Highlights
Tobacco smoking is the most common type of drug dependence worldwide (Anthony et al, 1994)
We evaluated the rats’ baseline locomotor activity
We evaluated the effects of the combination of RO5263397 and NIC on NIC sensitization retention because previous studies supported the hypothesis that pharmacological agents might reverse the sensitization to the locomotor effects of drugs (Li et al, 2000; Zhang et al, 2006, 2007; Carrera et al, 2011)
Summary
Tobacco smoking is the most common type of drug dependence worldwide (Anthony et al, 1994). The nicotine (NIC) contained in tobacco is the main reason for the development and maintenance of tobacco smoking (Stolerman and Jarvis, 1995), which is one of the principal risk factors for leading causes of human mortality, such as cancer, chronic obstructive pulmonary disease, and coronary heart disease (Murray and Lopez, 1997). In 2015, the World Health Organization estimated that more than 1.1 billion individuals smoked worldwide (World Health Organization, 2015). Estimates predict that approximately 1.5 to 1.9 billion individuals will be smokers in 2025. Current pharmacological approaches for tobacco smoking therapy are not sufficiently effective and mainly include substitution therapy. The current lack of methods to control NIC abuse has prompted researchers to search for new approaches
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