Summary: Manipulating newly identified pathways can reduce drug seeking behavior, a new study reports.
Source: University of New South Wales.
UNSW researchers have identified new brain pathways linked to addiction and shown that by manipulating them, drug seeking behaviour and motivation for alcohol can be reduced.
UNSW researchers have identified new brain pathways linked to addiction and shown that by manipulating them, drug seeking behaviour and motivation for alcohol can be reduced.
While the discovery was made in rats, it opens up a new target for developing treatments for drug and alcohol addiction in humans, which could include deep brain stimulation.
The study has been published in the Journal of Neuroscience.
Drug addiction is a chronic relapsing disorder characterised by cycles of drug abuse, abstinence and relapse.
“Current drug therapies are generally poor because we still don’t completely understand how the brain’s neural circuits contribute to different forms of relapse,” said first author of the study, Dr Asheeta Prasad from UNSW’s School of Psychology.
“Mapping these circuits is crucial if we are to move forward in treating drug and alcohol addiction,” Dr Prasad said.
The researchers studied the brain’s ventral pallidum (VP), which is responsible for regulating motivation, behaviour, and emotions.
Previous studies have shown that activity in the VP has been implicated in a variety of drugs of abuse including cocaine, amphetamines and alcohol. Importantly, VP is a key brain region for promoting relapse, with VP neurons activated during different forms of relapse.
The UNSW researchers identified for the first time that two distinct VP output brain pathways are necessary for different forms of alcohol-related relapse. They found that the brain pathways from the VP to the subthalamic nucleus, a small lens-shaped nucleus in the brain, and the ventral tegmental area, part of the mid-brain, are switched on during relapse behaviour. Their study has identified a novel node in the brain circuitry for relapse
When the researchers switched off these brain pathways, drug seeking behaviour and motivation for alcohol was reduced in rats.
The finding opens up the potential for using deep brain stimulation in the treatment of addiction.
“Deep brain stimulation of the subthalamic nucleus is currently used to manage Parkinson’s disease, but has not yet been tested in the treatment of addiction,” Dr Prasad said.
“It is a certainly a potential future treatment for relapsing disorders such as drug addiction and obesity.”
Source: Dan Wheelahan – University of New South Wales
Image Source: This NeuroscienceNews.com image is adapted from the University of New South Wales press release.
Original Research: Abstract for “Ventral Pallidum Output Pathways in Context-Induced Reinstatement of Alcohol Seeking” by Asheeta A. Prasad and Gavan P. McNally in Journal of Neuroscience. Published online November 16 2016 doi:10.1523/JNEUROSCI.2580-16.2016
[cbtabs][cbtab title=”MLA”]University of New South Wales. “Researchers Identify New Brain Pathways Linked to Addiction.” NeuroscienceNews. NeuroscienceNews, 25 November 2016.
<https://neurosciencenews.com/addiction-pathways-neuroscience-5597/>.[/cbtab][cbtab title=”APA”]University of New South Wales. (2016, November 25). Researchers Identify New Brain Pathways Linked to Addiction. NeuroscienceNews. Retrieved November 25, 2016 from https://neurosciencenews.com/addiction-pathways-neuroscience-5597/[/cbtab][cbtab title=”Chicago”]University of New South Wales. “Researchers Identify New Brain Pathways Linked to Addiction.” https://neurosciencenews.com/addiction-pathways-neuroscience-5597/ (accessed November 25, 2016).[/cbtab][/cbtabs]
Abstract
Ventral Pallidum Output Pathways in Context-Induced Reinstatement of Alcohol Seeking
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.
SIGNIFICANCE STATEMENT Ventral pallidum (VP) serves important roles in reward and motivation and is a critical node in the neural circuitry for reinstatement of drug seeking. Despite being a common locus for different forms of reinstatement, fundamental aspects of neural circuitry for these VP contributions to reinstatement of drug seeking remain unknown. Here we used a combination of neuroanatomical tracing and chemogenetic approaches to map the VP output pathways for context-induced reinstatement and reacquisition of alcohol seeking. We show that VP output pathways to the subthalamic nucleus and also to the ventral tegmental area are necessary for these forms of reinstatement.
“Ventral Pallidum Output Pathways in Context-Induced Reinstatement of Alcohol Seeking” by Asheeta A. Prasad and Gavan P. McNally in Journal of Neuroscience. Published online November 16 2016 doi:10.1523/JNEUROSCI.2580-16.2016
