Repetitive exposure to addictive drugs causes synaptic modification in the mesocorticolimbic dopamine (DA) system. Dopamine D1 receptors (D1R) or D2 receptors (D2R) expressed in the medium spiny neurons (MSNs) of the nucleus accumbens (NAc) play critical roles in the control of addictive behaviors. Optogenetic activation of D2R-expressing MSNs (D2R-MSNs) in the NAc previously demonstrated that these neurons play a key role in withdrawal-induced plasticity. Here, we examined the effect of optogenetic inhibition of D2R-MSNs in the NAc on cocaine-induced behavioral sensitization. Adeno-associated viral vectors encoding archaerhodopsin (ArchT) were delivered into the NAc of D2-Cre transgenic mice. Activation of ArchT produced photoinhibition of D2R-MSNs and caused disinhibition of neighboring MSNs in the NAc. However, such optogenetic silencing of D2R-MSNs in the NAc in vivo affected neither the initiation nor the expression of cocaine-induced behavioral sensitization. Similarly, photoinhibition of NAc D2R-MSNs in the NAc during the drug withdrawal period did not affect the expression of cocaine-induced behavioral sensitization. More detailed analysis of the effects of optogenetic activation of D2R-MSNs suggests that D2R-MSNs in the NAc exert important modulatory effects on neighboring MSN neurons, which may control the balanced output of NAc MSNs to control addictive behaviors.
Bibliographical noteFunding Information:
We thank staff of Gyerim Experimental Animal Resource Center for the animal care and technical assistance. We thank also Bokyeong Kim and Professor June-Seek Choi (Korea Univ.) for help and discussion. This work was supported by the Brain Research Program (to Ja-Hyun Baik; Grant No. 2013M3C7A1056101), by the Bio & Medical Technology Development Program (to Ja-Hyun Baik; Grant No. 2016M3A9D5A01952412), by Mid-Career Researcher Program (to Ja-Hyun Baik; Grant No. 2014R1A2A2A01003337) and by Science Research Center (to Ja-Hyun Baik; Grant No. 2015R1A5A1009024) through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT & Future Planning Republic of Korea, by a Korea University Grant (to Ja-Hyun Baik), by a grant from the World Class Institute (WCI) program of the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science, and Technology (MEST) (to George J. Augustine; No. WCI 2009-003), and by a CRP grant from the National Research Foundation of Singapore (to George J. Augustine).
© 2017 Federation of European Neuroscience Societies and John Wiley & Sons Ltd
- dopamine D2 receptors
- drug addiction
- medium spiny neurons
ASJC Scopus subject areas