Abstract
Ventral tegmental area (VTA) dopamine (DA) neurons perform diverse functions in motivation and cognition, but their precise roles in addiction-related behaviors are still debated. Here, we targeted VTA DA neurons for bidirectional chemogenetic modulation during specific tests of cocaine reinforcement, demand, and relapse-related behaviors in male rats, querying the roles of DA neuron inhibitory and excitatory G-protein signaling in these processes. Designer receptor stimulation of G q signaling, but not G s signaling, in DA neurons enhanced cocaine seeking via functionally distinct projections to forebrain limbic regions. In contrast, engaging inhibitory G i/o signaling in DA neurons blunted the reinforcing and priming effects of cocaine, reduced stress-potentiated reinstatement, and altered behavioral strategies for cocaine seeking and taking. Results demonstrate that DA neurons play several distinct roles in cocaine seeking, depending on behavioral context, G-protein-signaling cascades, and DA neuron efferent targets, highlighting their multifaceted roles in addiction.
Original language | English (US) |
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Pages (from-to) | 503-518 |
Number of pages | 16 |
Journal | Journal of Neuroscience |
Volume | 39 |
Issue number | 3 |
DOIs | |
State | Published - Jan 16 2019 |
Keywords
- Addiction
- Conditioned cues
- DREADDs
- Motivation
- Neural circuits
- Reinstatement
ASJC Scopus subject areas
- General Neuroscience