Study with rats suggests drinking alcohol increases risk of addiction to cocaine

November 2, 2017 by Bob Yirka, Medical Xpress report

A pile of cocaine hydrochloride. Credit: DEA Drug Enforcement Agency, public domain
(Medical Xpress)—A team of researchers working at Columbia University has found a possible link between prior use of alcohol and an increased risk of cocaine addiction. In their paper published on the open access site Science Advances, the group describes their study, what they found and why they believe more studies are required to better understand "gateway drugs."

Most everyone knows that is addictive, but few are aware that it is more addictive for some people than for others. Prior research has shown, for example, that just 21 percent of people who use cocaine become compulsive users. In this new effort, the researchers sought to learn more about the impact of so-called gateway drugs—drugs that lead people to take other, stronger drugs. More specifically, they wondered if alcohol might be a gateway to cocaine use and subsequent addiction.

To better understand the connection between and taking cocaine, the researchers enlisted the assistance of lab rats—some were given alcohol for 10 days and some were not, then both were given cocaine to see if prior exposure to alcohol impacted their desire for cocaine. The researchers found that it did; those rats that had been drinking prior to being given cocaine were clearly more interested in getting more. This was demonstrated by removing their resource, which was obtained by pressing the lever that normally delivered cocaine. Those rats that were not given alcohol before the cocaine kept pressing the lever on average 18 times. In sharp contrast, those that had been given alcohol pressed the lever on average 58 times—they were also more willing to endure pain to get it. This was shown by attaching a device that delivered a mild shock—those given alcohol were found willing to endure jolts as strong as 0.3 mA to get their fix.

The researchers also found a physical cause for the increased desire for the drug—the brains of those rats that had consumed for 10 days had reduced levels of two proteins that normally serve as a brake on reward circuitry. With reduced levels of these proteins, the rats had no reason to resist the pleasure the gave them.

Explore further: Male rats found to pass on epigenetic susceptibility to cocaine addiction to offspring

More information: Edmund A. Griffin et al. Prior alcohol use enhances vulnerability to compulsive cocaine self-administration by promoting degradation of HDAC4 and HDAC5, Science Advances (2017). DOI: 10.1126/sciadv.1701682

Abstract
Addiction to cocaine is commonly preceded by experiences with legal or decriminalized drugs, such as alcohol, nicotine, and marijuana. The biological mechanisms by which these gateway drugs contribute to cocaine addiction are only beginning to be understood. We report that in the rat, prior alcohol consumption results in enhanced addiction-like behavior to cocaine, including continued cocaine use despite aversive consequences. Conversely, prior cocaine use has no effect on alcohol preference. Long-term, but not short-term, alcohol consumption promotes proteasome-mediated degradation of the nuclear histone deacetylases HDAC4 and HDAC5 in the nucleus accumbens, a brain region critical for reward-based memory. Decreased nuclear HDAC activity results in global H3 acetylation, creating a permissive environment for cocaine-induced gene expression. We also find that selective degradation of HDAC4 and HDAC5, facilitated by the class II–specific HDAC inhibitor MC1568, enhances compulsive cocaine self-administration. These results parallel our previously reported findings that the gateway drug nicotine enhances the behavioral effects of cocaine via HDAC inhibition. Together, our findings suggest a shared mechanism of action for the gateway drugs alcohol and nicotine, and reveal a novel mechanism by which environmental factors may alter the epigenetic landscape of the reward system to increase vulnerability to cocaine addiction.

Related Stories

Male rats found to pass on epigenetic susceptibility to cocaine addiction to offspring

May 31, 2017
(Medical Xpress)—A team of researchers with Fudan University in China has found that male rats are able to pass on their susceptibility to cocaine addiction through non-genetic means. In their paper published in the journal ...

Activating brain region creates intense desire to use cocaine

August 22, 2017
Researchers have identified a portion of the brain that intensifies one's desire for certain rewards—in this case, mimicking addiction to cocaine.

Are weight loss drugs the next tool to combat cocaine addiction?

September 20, 2017
Boston Medical Center's (BMC) psychiatry team is studying a drug called lorcaserin, which targets the brain's serotonin receptors and could help reduce cocaine cravings as well as dampen the rewards associated with taking ...

Researchers find brain region that affects drug use habits

June 27, 2017
The human brain is nimble. It can reorganize itself to learn new things, catalog memories, and even break old habits. So, what if our brains could be taught to suppress cravings, especially the destructive impulse to use ...

Treating cocaine addiction by reducing our appetite for drugs?

March 16, 2017
The hypocretin/orexin (HCRT) system of the brain is best known for promoting wakefulness and appetite. A new paper in Biological Psychiatry suggests that blocking hypocretin signaling via the HCRT-1 receptor (HCRT-R1) might ...

In rats that can't control glutamate, cocaine is less rewarding, staving off relapse

July 11, 2017
Rats missing a neuroreceptor that controls the release of the neurotransmitter glutamate are less amenable to the rewarding effects of cocaine, increasing their chance of kicking the habit once addicted, researchers from ...

Recommended for you

Classifying brain microglia: Which are good and which are bad?

December 6, 2018
Microglia are known to be important to brain function. The immune cells have been found to protect the brain from injury and infection and are critical during brain development, helping circuits wire properly. They also seem ...

Drawing is better than writing for memory retention

December 6, 2018
Older adults who take up drawing could enhance their memory, according to a new study.

Friend or foe? Brain area that controls social memory also triggers aggression

December 5, 2018
Columbia scientists have identified a brain region that helps tell an animal when to attack an intruder and when to accept it into its home. This brain area, called CA2, is part of the hippocampus, a larger brain structure ...

How the brain hears and fears

December 5, 2018
How is it that a sound can send a chill down your spine? By observing individual brain cells of mice, scientists at Cold Spring Harbor Laboratory (CSHL) are understanding how a sound can incite fear.

Adding new channels to the brain remote control

December 5, 2018
By enabling super-fast remote control of specific cells, light-activated proteins allow researchers to study the function of individual neurons within a large network—even an entire brain. Now one of the pioneers of 'optogenetics' ...

Microbial-based treatment reverses autism spectrum social deficits in mouse models

December 4, 2018
An unconventional approach has successfully reversed deficits in social behaviors associated with autism spectrum disorders (ASD) in genetic, environmental and idiopathic mouse models of the condition. Researchers at Baylor ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.