Brain mechanism linked to relapse after cocaine withdrawal

Sep 08, 2010

Addictive drugs are known to induce changes in the brain's reward circuits that may underlie drug craving and relapse after long periods of abstinence. Now, new research, published by Cell Press in the September 9 issue of the journal Neuron, uncovers a specific neural mechanism that may be linked to persistent drug-seeking behavior and could help to guide strategies for development of new therapies for cocaine addiction.

Previous research has shown that the ventral tegmental area (VTA) is a brain region that is activated when cocaine users experience a craving for cocaine after being exposed to cocaine-associated cues. The medial prefrontal cortex (mPFC), which receives input from the VTA via circuits that use the "reward" neurotransmitter dopamine, has also been implicated in drug craving after cocaine withdrawal. Further, increases in the level of brain-derived neurotrophic factor (BDNF) have been observed in the VTA and mPFC in rats after withdrawal from repeated cocaine exposure.

"BDNF plays a key role in modulating the structure and function of synapses, the sites of communication between neurons. Therefore, increased BDNF after cocaine withdrawal may drive synaptic changes that contribute to compulsive drug seeking behavior," explains senior author, Dr. Mu-ming Poo from the University of California, Berkeley. "It has been shown that increased BDNF in the VTA after cocaine withdrawal in rats promotes the drug-dependent motivational state. However, nothing is known about the potential BDNF effect on synaptic function and plasticity in mPFC neurons after cocaine withdrawal."

Dr. Poo and colleagues designed a study to examine how BDNF and the mPFC might contribute to relapse after . The researchers found that the gradual increase in BDNF expression in the rat mPFC after terminating repeated cocaine exposure significantly enhanced the activity-induced potentiation of specific synapses. Dr. Poo's group went on to uncover the specific cellular mechanism linking increased BDNF with enhanced synaptic plasticity and demonstrated that interference with the key molecule in the BDNF signaling process reduced behavioral sensitivity after cocaine withdrawal in rats.

"In short, our results demonstrate that elevated BDNF expression after cocaine withdrawal sensitizes the excitatory in the mPFC to undergo activity-induced persistent potentiation that may contribute to cue-induced drug cravings and drug-seeking behavior," concludes Dr. Poo. Although a clear correlation between rat and human behaviors of cocaine craving and relapse remains to be established, the uncovered in this study does appear to have behavioral relevance and may represent a direct brain sensitization that is involved in triggering relapse.

Explore further: Steering the filaments of the developing brain

add to favorites email to friend print save as pdf

Related Stories

Brain's reaction to self-administered cocaine differs

Jul 30, 2008

New research has uncovered a fundamental cellular mechanism that may drive pathological drug-seeking behavior. The study, published by Cell Press in the July 31 issue of the journal Neuron, examines the brain's reward circui ...

Cocaine cravings are studied

Jun 15, 2006

U.S. scientists say they have found the brain chemistry that underlies "cue-induced" craving in cocaine addicts.

Cocaine-linked genes enhance behavioral effects of addiction

May 13, 2009

New research sheds light on how cocaine regulates gene expression in a crucial reward region of the brain to elicit long-lasting changes in behavior. The study, published by Cell Press in the May 14th issue of the journal ...

Recommended for you

Steering the filaments of the developing brain

12 hours ago

During brain development, nerve fibers grow and extend to form brain circuits. This growth is guided by molecular cues (Fig. 1), but exactly how these cues guide axon extension has been unclear. Takuro Tojima ...

Do we really only use 10% of our brain?

13 hours ago

As the new film Lucy, starring Scarlett Johansson and Morgan Freeman is set to be released in the cinemas this week, I feel I should attempt to dispel the unfounded premise of the film – that we only use 10% of our brains ...

Birthday matters for wiring-up the brain's vision centers

Jul 31, 2014

Researchers at the University of California, San Diego School of Medicine have evidence suggesting that neurons in the developing brains of mice are guided by a simple but elegant birth order rule that allows them to find ...

User comments : 0