Role of dopamine projections from ventral tegmental area to nucleus accumbens and medial prefrontal cortex in reinforcement behaviors assessed using optogenetic manipulation

• Published in: Metabolic brain disease 2017-10, Vol.32 (5), p.1491-1502
• Main Authors: Han, Xiao, Jing, Man-yi, Zhao, Tai-yun, Wu, Ning, Song, Rui, Li, Jin
• Format: Article
• Language: English
• Subjects: Amphetamines; Animal behavior; Animals; Behavior, Animal - physiology; Biochemistry; Biomedical and Life Sciences; Biomedicine; Conditioning, Operant - drug effects; Conditioning, Operant - physiology; Dopamine; Dopamine Agents - administration & dosage; Dopamine Agents - pharmacology; Dopamine Plasma Membrane Transport Proteins - genetics; Dopamine transporter; Dopaminergic Neurons - physiology; Dose-Response Relationship, Drug; Excitation; Forecasting; Locomotion; Male; Metabolic Diseases; Methamphetamine; Methamphetamine - administration & dosage; Methamphetamine - pharmacology; Mice; Mice, Transgenic; Motor Activity - drug effects; Mouse devices; Neural Pathways - diagnostic imaging; Neural Pathways - physiology; Neurology; Neurons; Neurosciences; Nuclei; Nucleus accumbens; Nucleus Accumbens - diagnostic imaging; Nucleus Accumbens - physiology; Oncology; Opsins; Optogenetics; Original Article; Pharmacology; Photic Stimulation; Prefrontal cortex; Prefrontal Cortex - diagnostic imaging; Prefrontal Cortex - physiology; Reinforcement; Rodents; Self Stimulation; Stimulation; Transgenic mice; Ventral Tegmental Area - diagnostic imaging; Ventral Tegmental Area - physiology; Ventral tegmentum
• ISSN: 0885-7490; 1573-7365
• DOI: 10.1007/s11011-017-0023-3

Dopamine (DA) neurons in the ventral tegmental area (VTA) are predicted to play important roles in reward. In pharmacological studies, the rewarding effects of methamphetamine are mediated by DA neurons localized in the VTA. The nucleus accumbens (NAc) and medial prefrontal cortices (mPFC) are the main projections from the VTA. However, the role of these projections remains unclear, particularly the mPFC projections. In the present study, DAT-Cre transgenic mice received an injection of adeno-associated viral vectors encoding channelrhodopsin2 (ChR2) or control vector into the VTA resulting in the selective expression of these opsins in DA neurons. Then, we stimulated the VTA, NAc (core and shell) or mPFC (prelimbic cortex (PL) and infralimbic cortex (IL)) via an optical fiber. The mice with ChR2 learned instrumental responses corresponding to the delivery of photostimulation into the VTA. The projections to the NAc core and shell from the VTA and stimulation of the NAc subregion both induced reinforcement. For projections to the mPFC (IL and PL), we verified that stimulation of the IL induced reinforcement dependent on DA from the VTA but not the PL. Furthermore, micro-infusion of methamphetamine into the NAc core and NAc shell also induced hyper-locomotion in a dose-dependent manner with a slight tendency of increased excitation of the IL but not PL. Taken together, excitation of the projection into the NAc core, NAc shell and IL elicited positive behavior during reward.