Role of trace amine-associated receptor 1 in nicotine's behavioral and neurochemical effects
| Autor: | Jinwoo Park, Jun-Xu Li, Yanan Zhang, Justin N. Siemian, David M. Dietz, Jian-Feng Liu, Robert Seaman, Bernard Johnson, Rohan V. Bhimani, Marius C. Hoener, Qing Zhu |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Male Nicotine Self Administration Striatum Pharmacology Nucleus accumbens Nucleus Accumbens Article Receptors G-Protein-Coupled Rats Sprague-Dawley 03 medical and health sciences 0302 clinical medicine Neurochemical Dopamine TAAR1 medicine Animals Nicotinic Agonists Oxazoles Chemistry Dopaminergic Rats Psychiatry and Mental health 030104 developmental biology Gene Knockdown Techniques Conditioning Operant Self-administration 030217 neurology & neurosurgery medicine.drug |
| Zdroj: | Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology. 43(12) |
| ISSN: | 1740-634X |
| Popis: | Nicotine addiction and abuse remains a global health issue. To date, the fundamental neurobiological mechanism of nicotine addiction remains incompletely understood. Trace amine-associated receptor 1 (TAAR1) is thought to directly modulate dopaminergic system and are thought to be a neural substrate underlying addictive-like behaviors. We aimed to investigate the role of TAAR1 in nicotine addictive-like behaviors. TAAR1 expression after nicotine treatment was evaluated by western blotting. c-Fos immunofluorescence and in vivo fast-scan cyclic voltammetry were used to examine the activation of brain regions and dopamine release, respectively. We then thoroughly and systematically examined the role of TAAR1 in mediating nicotine-induced sensitization, nicotine discrimination, nicotine self-administration, nicotine demand curve, and the reinstatement of nicotine-seeking. Local pharmacological manipulation was conducted to determine the role of TAAR1 in the nucleus accumbens (NAcs) in the reinstatement of nicotine-seeking. We found that the expression of TAAR1 protein was selectively downregulated in the NAc, with no change in either dorsal striatum or prefrontal cortex. TAAR1 activation was sufficient to block nicotine-induced c-Fos expression in the NAc, while also reducing nicotine-induced dopamine release in the NAc. Systemic administration of TAAR1 agonists attenuated the expression and development of nicotine-induced sensitization, nicotine self-administration, the reinstatement of nicotine-seeking, and increased the elasticity of nicotine demand curve, while intra-NAc infusions of a TAAR1 agonist was sufficient to attenuate nicotine reinstatement. Moreover, TAAR1-knockout rats showed augmented cue-induced and drug-induced reinstatement of nicotine-seeking. These results indicated that modulation of TAAR1 activity regulates nicotine addictive-like behaviors and TAAR1 represents a novel target towards the treatment of nicotine addiction. |
| Databáze: | OpenAIRE |
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