Cortical control of VTA function and influence on nicotine reward.
Tobacco use is a major public health problem. Nicotine acts on widely distributed nicotinic acetylcholine receptors (nAChRs) in the brain and excites dopamine (DA) neurons in the ventral tegmental area (VTA). The elicited increase of DA neuronal activity is thought to be an important mechanism for nicotine reward and subsequently the transition to addiction. However, the current understanding of nicotine reward is based predominantly on the data accumulated from in vitro studies, often from VTA slices. Isolated VTA slices artificially terminate communications between neurons in the VTA and other brain regions that may significantly alter nicotinic effects. Consequently, the mechanisms of nicotinic excitation of VTA DA neurons under in vivo conditions have received only limited attention. Building upon the existing knowledge acquired in vitro, it is now time to elucidate the integrated mechanisms of nicotinic reward on intact systems that are more relevant to understanding the action of nicotine or other addictive drugs. In this review, we summarize recent studies that demonstrate the impact of prefrontal cortex (PFC) on the modulation of VTA DA neuronal function and nicotine reward. Based on existing evidence, we propose a new hypothesis that PFC-VTA functional coupling serves as an integration mechanism for nicotine reward. Moreover, addiction may develop due to nicotine perturbing the PFC-VTA coupling and thereby eliminating the PFC-dependent cognitive control over behavior.
Divisions of Neurology, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, AZ 85013-4496, USA; Departments of Physiology, Shantou University Medical College, Shantou, Guangdong, China. Electronic address: Jie.Wu@DignityHealth.org.
Jie
J
Wu
Ming
M
Gao
Jian-Xin
JX
Shen
Wei-Xing
WX
Shi
Andrew M
AM
Oster
Boris S
BS
Gutkin
D005786:Gene Expression Regulation; D006801:Humans; D009538:Nicotine / Q000494:pharmacology*; D017397:Prefrontal Cortex / Q000502:physiology*; D011978:Receptors, Nicotinic / Q000235:genetics / Q000378:metabolism*; D017557:Ventral Tegmental Area / Q000502:physiology*
D011978:Receptors, Nicotinic; D009538:Nicotine
ACh; DA; Dopamine neurons; Nicotine reward; Nicotinic acetylcholine receptor; PFC; Prefrontal cortex; VTA; Ventral tegmental area; acetylcholine; dopamine; nAChR(s); nicotinic acetylcholine receptor(s); prefrontal cortex; ventral tegmental area