TY - JOUR

T1 - Trace amine-associated receptor 1 modulates the locomotor and sensitization effects of nicotine

AU - Sukhanov, Ilya

AU - Dorofeikova, Mariia

AU - Dolgorukova, Antonina

AU - Dorotenko, Artem

AU - Gainetdinov, Raul R.

PY - 2018/4/6

Y1 - 2018/4/6

N2 - 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.

AB - 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.

KW - Dopamine

KW - Drug addiction

KW - Locomotor activity

KW - Nicotine

KW - Sensitization

KW - TAAR1

KW - nicotine

KW - drug addiction

KW - DOPAMINERGIC SYSTEM

KW - RATS

KW - AGONISTS

KW - REWARD

KW - REVERSAL

KW - MONOAMINERGIC NEUROTRANSMISSION

KW - MICE LACKING TAAR1

KW - locomotor activity

KW - COCAINE BEHAVIORAL SENSITIZATION

KW - sensitization

KW - dopamine

KW - AMPHETAMINE

KW - BRAIN

UR - http://www.scopus.com/inward/record.url?scp=85045072730&partnerID=8YFLogxK

UR - http://www.mendeley.com/research/trace-amineassociated-receptor-1-modulates-locomotor-sensitization-effects-nicotine

U2 - 10.3389/fphar.2018.00329

DO - 10.3389/fphar.2018.00329

M3 - Article

AN - SCOPUS:85045072730

VL - 9

JO - Frontiers in Pharmacology

JF - Frontiers in Pharmacology

SN - 1663-9812

IS - APR

M1 - 329

ER -