Cocaine Addiction Linked To Structure In Prefrontal Cortex, Which Plays A Role In Memory

Pyramidal neurons in the prefrontal cortex play a role in drug addiction. If these neurons could be disabled, drug-taking might become less compulsive. Valerie Everett, CC by 2.0

Why do addicts compulsively return to their drug of choice even if it has caused them tremendous pain and countless losses? Memory plays a powerful role in the cycle of addiction; it provides the motivation for continued use and for relapse after rehab. In drug addiction, say researchers from Washington State University, pyramidal neurons in the medial prefrontal cortex play an important role in forming memories. If these neurons could be disabled, drug-taking just might become less compulsive.

Our brains are wired to make sure that we will repeat life-sustaining activities, such as eating and sex. Our brains do this by activating the reward circuit so that we wake up and take note that something important is happening. It is pleasure linked to memory, then, that teaches us how to take care of ourselves by doing the same activities again and again without thinking.

Drugs stimulate the exact same reward circuit, yet their impact is amplified up to 10 times (in some cases). And so drug memories can become so powerful they soon dominate the entire system of rewards, usurping our natural hierarchy of needs. This is how drugs replace a person’s desire for food, sex, and ultimately human dignity.

For the current study, Dr. Barbara Sorg, a professor of neuroscience at Washington State University, and her colleagues conditioned male rates within a special "drug cage." Time and again the rats were given cocaine in that specific setting, and with each new experience, their memories of that cage became more enriched. Associating their pleasant drug-fueled experiences with this special place, the rat’s memories were reconsolidated and reinforced each time they took the drug and whenever they visited the cage.

After dividing the rats into two groups, the researchers removed structures called perineuronal nets in one group, while leaving the other as is. Perineuronal nets are a condensed and stable matrix, which surround the synapses and dendrites of neurons in the the medial prefrontal cortex. This area of the brain is involved in learning, attention, cognition, and inhibitory behavior, as well as memory. The nets are believed to play a key role in brain plasticity and also to strengthen or weaken memories.

Testing the rats, the researchers discovered those with their nets removed were less interested in the drug cage than the untouched group. In fact, they displayed poorer memories.

Sorg believes the procedure probably did not erase the drug memory but blunted its emotional power. Her discovery opens the door to developing new therapy targets to counteract cocaine's influence over memories. For instance, it might be possible to deconstruct the net by, say, destroying a single protein involved in their construction.

Source: Slaker M, Churchill L, Rodd RP, et al.  Removal of Perineuronal Nets in the Medial Prefrontal Cortex Impairs the Acquisition and Reconsolidation of a Cocaine-Induced Conditioned Place Preference Memory. Journal of Neuroscience. 2015.

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