Rutgers Scientists Pinpoint Brain Cells Involved In Drug Addiction Relapse

Long after an addict has become drug-free, simple events or circumstances that were associated with prior drug use, such as walking through a particular neighborhood or hearing a particular song, can reawaken memories that trigger a craving and provoke a relapse. These environmental stimuli may render an addict vulnerable to a return to compulsive drug use.

"We've identified a part of the brain that appears to process these memories," said Rutgers psychology professor Mark West. "This might be one of the brain areas that a very skilled pharmacological approach could target."

West and his Rutgers colleagues published their findings in the Aug. 13 issue of the Journal of Neuroscience. They concentrated their work on nerve cells or neurons in the nucleus accumbens, a brain region known to be involved in the addictive effects of drugs.

They were searching for those nerve cells that respond to a drug-associated environmental stimulus. The laboratory work employed a design, previously demonstrated to be a good model of human addiction, in which rats were able to self-administer a specific drug. The animals were provided cocaine, one of the most highly addictive narcotics, dispensed to them when they pressed a lever. Microelectrodes that recorded the activity of single neurons were used to monitor nerve cells in a part of the nucleus accumbens known as the shell.

As the animals self-administered the cocaine, a tone was sounded and they came to associate the tone with the drug. If an animal pressed the lever in the absence of the tone, no cocaine was dispensed. At the end of three weeks, the rats had learned to press the lever when they heard the tone. Next, both the drug and the lever were removed. After a month, the lever – but no cocaine – was returned to the cage but was virtually ignored by the animals – until the tone was again sounded.

"When we started to play the tone that had been paired with cocaine, the animals began to press the lever at a fairly high rate," said West. "It indicated that the animals had a persistent memory – they remembered the significance of the tone. We interpreted the resumption of lever pressing as a behavioral relapse." During this relapse of drug seeking, brain activity recordings showed that accumbens shell neurons responded almost instantaneously when the tone was sounded. In contrast, accumbens neurons had not responded to the tone before conditioning.

Eventually the animals gave up pressing the lever, even in the presence of the tone, since no cocaine was forthcoming. "Even though the lever pressing behavior was extinguished, we were still seeing accumbens neuron activity in response to the tone," said West.

West explained that the brain is slow to forget the stimuli. After a relatively long period of drug abstinence, the persistence of the memories – those conditioned associations reflected in the neural activity – may partially explain why treating drug addiction is an uphill battle, West observed.

"The neural mechanisms of learning are still not understood. This is what we were investigating here – neural mechanisms in one part of a brain circuit that participate in creating memories of these environmental stimuli," said West. "As medical science seeks to develop chemicals that alleviate drug craving, our data may help scientists or clinicians know what part of the brain to target. With cocaine, we haven't yet discovered a magic bullet that can go in and just cure the problem."