Previous studies show that activation and suppression of dopamine systems elicit reward and aversion respectively. These effects are usually attributed to dopamine neurons in the ventral tegmental area (VTA) and the mesolimbic dopamine system. On the other hand, dopamine neurons in the substantia nigra pars compacta (SNc) and the nigrostriatal system often linked with motor and cognitive control, including the learning of stimulus-response associations. Here we show that excitation and inhibition of dopamine neurons in the SNc elicit reward and aversion. TH-Cre transgenic mice received adeno-associated viral vectors encoding channelrhodopsin2 (ChR2), halorhodopsin (NpHR), or no opsin into the VTA or SNc. Mice with ChR2 quickly learned to respond on the lever that delivered light into the VTA or SNc. And, when the assignment of active and inactive levers was changed, they shifted their lever preference. They also showed place preference to the compartment in which they concurrently received intracranial light. In addition, mice with NpHR avoided the compartment in which they concurrently received intracranial light into the VTA or SNc, while control mice did not. Our findings confirm that the excitation and inhibition of SNc dopamine neurons induces reward and aversion similar to the VTA dopamine neurons. The present data challenge the dichotomous notion that affective processes are mediated by dopamine neurons in the VTA, but not SNc and suggest the role of nigrostriatal projections in motivation and affect. Therefore, SNc dopamine neurons may play motivational and affective aspects of drug addiction such as craving and those of Parkinsons patients (i.e., depression, anhedonia, and apathy).

Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
National Institute on Drug Abuse
Zip Code
Ikemoto, Satoshi; Yang, Chen; Tan, Aaron (2015) Basal ganglia circuit loops, dopamine and motivation: A review and enquiry. Behav Brain Res 290:17-31
Ikemoto, Satoshi; Bonci, Antonello (2014) Neurocircuitry of drug reward. Neuropharmacology 76 Pt B:329-41
Keller, Kristine L; Vollrath-Smith, Fiori R; Jafari, Mehrnoosh et al. (2014) Synergistic interaction between caloric restriction and amphetamine in food-unrelated approach behavior of rats. Psychopharmacology (Berl) 231:825-40
Ilango, Anton; Kesner, Andrew J; Keller, Kristine L et al. (2014) Similar roles of substantia nigra and ventral tegmental dopamine neurons in reward and aversion. J Neurosci 34:817-22
Ilango, Anton; Kesner, Andrew J; Broker, Carl J et al. (2014) Phasic excitation of ventral tegmental dopamine neurons potentiates the initiation of conditioned approach behavior: parametric and reinforcement-schedule analyses. Front Behav Neurosci 8:155
Jhou, Thomas C; Good, Cameron H; Rowley, Courtney S et al. (2013) Cocaine drives aversive conditioning via delayed activation of dopamine-responsive habenular and midbrain pathways. J Neurosci 33:7501-12