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Activating Brain Region Creates Intense Desire to Use Cocaine

Summary: Using optogenetics to stimulate the amygdala, researchers intensify the desire to consume cocaine in rats.

Source: University of Michigan.

Researchers have identified a portion of the brain that intensifies one’s desire for certain rewards—in this case, mimicking addiction to cocaine.

The new University of Michigan study found that activating part of the amygdala, an almond-shaped brain region, intensifies motivation to consume cocaine far beyond ordinary drug levels, similar to its ability to intensify motivation for sweet foods such as sugar.

“This would suggest that the amygdala plays a key role in drug addiction,” said Shelley Warlow, a U-M psychology graduate student and the study’s lead author.

In addiction, drugs become the sole object of desire. Yet many people try drugs without becoming addicted and lead normal lives pursuing a healthy balance of different rewards, or even giving up drugs entirely.

However, for addicts, drugs become so attractive as to cause intense motivation focused entirely on obtaining drugs at the expense of other normal life rewards.

“Understanding brain areas and the mechanisms involved in this intense motivation will be important in developing treatments for addiction and other compulsive disorders,” Warlow said.

Researchers first implanted rats with a catheter that allowed them to earn doses of cocaine by poking their noses into small holes in the wall.

Whenever rats would poke their nose into one particular hole to earn intravenous cocaine, a laser light would also painlessly activate the neurons in the central amygdala at the same time. Poking their nose into a different hole earned identical cocaine, but never activated the amygdala.

Image shows a white rat.

Researchers identified a portion of the brain that intensified the desire for certain rewards, such as cocaine. In the experiments, rats had to choose between two cocaine rewards by poking their noses through small holes in a wall. NeuroscienceNews.com image is credited to Shelley Warlow.

When able to freely choose between those two cocaine rewards, rats focused only on the port that earned cocaine together with amygdala-activating laser, consumed much more cocaine than rats without amygdala activation, and avidly nibbled around the laser-cocaine hole as though seeking more. Rats were also willing to work almost three times harder for the cocaine when paired with amygdala activation, the study indicated.

Rats appeared to be indifferent to amygdala laser activation when offered by itself. The amygdala activation only intensified motivation when cocaine was also present. By contrast, when the researchers temporarily inactivated the amygdala using a painless drug infusion, rats completely stopped responding for cocaine altogether.

About this neuroscience research article

The study, which appears in the Journal of Neuroscience, was also conducted by Mike Robinson, assistant professor of psychology and neuroscience at Wesleyan University, and Kent Berridge, U-M’s James Olds Distinguished University Professor of Psychology and Neuroscience. The National Institute on Drug Abuse funded the research.

Source: Jared Wadley – University of Michigan
Image Source: NeuroscienceNews.com image is credited to Shelley Warlow.
Original Research: Abstract for “Optogenetic central amygdala stimulation intensifies and narrows motivation for cocaine” by Shelley M. Warlow, Mike J.F. Robinson and Kent C. Berridge in Journal of Neuroscience. Published online July 27 2017 doi:10.1523/JNEUROSCI.3141-16.2017

Cite This NeuroscienceNews.com Article
University of Michigan ” Activating Brain Region Creates Intense Desire to Use Cocaine.” NeuroscienceNews. NeuroscienceNews, 22 August 2017.
<http://neurosciencenews.com/cocaine-amygdala-activation-7350/>.
University of Michigan (2017, August 22). Activating Brain Region Creates Intense Desire to Use Cocaine. NeuroscienceNew. Retrieved August 22, 2017 from http://neurosciencenews.com/cocaine-amygdala-activation-7350/
University of Michigan ” Activating Brain Region Creates Intense Desire to Use Cocaine.” http://neurosciencenews.com/cocaine-amygdala-activation-7350/ (accessed August 22, 2017).

Abstract

Optogenetic central amygdala stimulation intensifies and narrows motivation for cocaine

Addiction is often characterized by intense motivation for a drug, which may be narrowly focused at the expense of other rewards. Here we examined the role of amygdala-related circuitry in the amplification and narrowing of motivation focus for intravenous cocaine. We paired optogenetic channelrhodopsin (ChR2) stimulation in either central nucleus of amygdala (CeA) or basolateral amygdala (BLA) of female rats with one particular nosepoke-porthole option for earning cocaine infusions (0.3 mg/kg, i.v.). A second alternative porthole earned identical cocaine but without ChR2 stimulation. Consequently, CeA rats quickly came to intensely and exclusively pursue their CeA ChR2-paired cocaine option, elevating cocaine intake, while ignoring their alternative cocaine alone option. By comparison, BLA ChR2 pairing failed to enhance cocaine motivation. CeA rats also emitted consummatory bites toward their laser-paired porthole, suggesting higher incentive salience made that cue more attractive. A separate progressive ratio test of incentive motivation confirmed that CeA ChR2 amplified rats’ motivation, raising their breakpoint effort price for cocaine by 10-fold. However, CeA ChR2 laser on its own lacked any reinforcement value: laser by itself was never self-stimulated, not even by the same rats in which it amplified motivation for cocaine. Conversely, CeA inhibition by muscimol/baclofen microinjections prevented acquisition of cocaine self-administration and laser preference, while CeA inhibition by optogenetic halorhodopsin suppressed cocaine intake, indicating CeA circuitry is needed for ordinary cocaine motivation. We conclude that CeA ChR2 excitation paired with a cocaine option specifically focuses and amplifies motivation to produce intense pursuit and consumption focused on that single target.

SIGNIFICANCE STATEMENT

In addiction, intense incentive motivation often becomes narrowly focused on a particular drug of abuse. Here we show that pairing CeA optogenetic stimulation with one option for earning intravenous cocaine makes that option the almost exclusive focus of intense pursuit and consumption. CeA stimulation also elevated the effort cost rats were willing to pay for cocaine, and made associated cues become intensely attractive. However, we also show CeA laser had no reinforcing properties at all when given alone for the same rats. Thus, CeA laser pairing makes its associated cocaine option and cues become powerfully attractive in a nearly addictive-like fashion.

“Optogenetic central amygdala stimulation intensifies and narrows motivation for cocaine” by Shelley M. Warlow, Mike J.F. Robinson and Kent C. Berridge in Journal of Neuroscience. Published online July 27 2017 doi:10.1523/JNEUROSCI.3141-16.2017

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