Modulation of Nicotine-Associated Behaviour in Rats By μ-Opioid Signals from the Medial Prefrontal Cortex to the Nucleus Accumbens Shell
Feng Zhu1 · Hirosato Kanda3 · Hiroyuki Neyama4 · Yuping Wu4 · Shigeki Kato5 · Di Hu4 · Shaoqi Duan1 · Koichi Noguchi1 · Yasuyoshi Watanabe4 · Kazuto Kobayashi5 · Yi Dai1 · Yilong Cui1,2,41 Department of Anatomy and Neuroscience, Hyogo Medical University, Nishinomiya, Hyogo 663-8501, Japan
2 Laboratory for Brain-Gut Homeostasis, Hyogo Medical University, Nishinomiya, Hyogo 663-8501, Japan
3 School of Pharmacy, Hyogo Medical University, Kobe, Hyogo 650-8530, Japan
4 RIKEN Center for Biosystems Dynamics Research, Kobe, Hyogo 650-0047, Japan
5 Department of Molecular Genetics, Fukushima Medical University Institute of Biomedical Sciences, Fukushima 960-1295, Japan
Abstract
Nicotine addiction is a concern worldwide. Most mechanistic investigations are on nicotine substance dependence properties based on its pharmacological effects. However, no effective therapeutic treatment has been established. Nicotine addiction is reinforced by environments or habits. We demonstrate the neurobiological basis of the behavioural aspect of nicotine addiction. We utilized the conditioned place preference to establish nicotine-associated behavioural preferences (NABP) in rats. Brain-wide neuroimaging analysis revealed that the medial prefrontal cortex (mPFC) was activated and contributed to NABP. Chemogenetic manipulation of µ-opioid receptor positive (MOR+) neurons in the mPFC or the excitatory outflow to the nucleus accumbens shell (NAcShell) modulated the NABP. Electrophysiological recording confirmed that the MOR+ neurons directly regulate the mPFC-NAcShell circuit via GABAA receptors. Thus, the MOR+ neurons in the mPFC modulate the formation of behavioural aspects of nicotine addiction via direct excitatory innervation to the NAcShell, which may provide new insight for the development of effective therapeutic strategies.
Keywords
Nicotine-associated behaviour; μ-Opioid receptor; Medial prefrontal cortex; Nucleus accumbens shell; Small-animal neuroimaging
