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- Title
Ventral Pallidum Output Pathways in Context-Induced Reinstatement of Alcohol Seeking.
- Authors
Prasad, Asheeta A.; McNally, Gavan P.
- Abstract
Ventral pallidum (VP) is a well-established locus for the reinforcing effects of drugs of abuse and reinstatement of drug seeking. However, VP neurons are at the origin of multiple output pathways, with strong projections to ventral tegmental area (VTA), subthalamic nucleus (STN), lateral hypothalamus, among others, and the roles of these VP output pathways in reinstatement of drug seeking remain poorly understood. Here we addressed these issues using a combination of neuroanatomical tracing and chemogenetic approaches. First, using dual-retrograde tracing, we show that VP neurons projecting to either VTA or STN are recruited during context-induced reinstatement of extinguished alcohol seeking in rats. Then, using chemogenetics, we show modulation of context-induced reinstatement and reacquisition of alcohol seeking via designer receptors exclusively activated by designer drugs excitation or inhibition of the VP. To determine the causal roles of VP → VTA and VP → STN pathways in context-induced reinstatement and reacquisition we used a chemogenetic disconnection approach and show that silencing either the VP → VTA or VP → STN pathways is sufficient to reduce both reinstatement and reacquisition of alcohol seeking. Moreover, these disconnections also each reduced responding and motivation during a progressive ratio test but had no effect on locomotor activity. Together, these results show that multiple ventral pallidal output pathways contribute to relapse to alcohol seeking.
- Subjects
GLOBUS pallidus; GAIT disorders; DRUG abuse prevention; SUBTHALAMIC nucleus; HYPOTHALAMUS injuries; COMPLICATIONS of alcoholism; DISEASE risk factors
- Publication
Journal of Neuroscience, 2016, Vol 36, Issue 46, p11716
- ISSN
0270-6474
- Publication type
Article
- DOI
10.1523/JNEUROSCI.2580-16.2016