Cocaine-induced brain plasticity may protect the addicted brain

Aug 27, 2008

A new study has unraveled some of the mysteries of the cocaine-addicted brain and may pave the way for the design of more effective treatments for drug addiction. The research, published by Cell Press in the August 28 issue of the journal Neuron, identifies specific brain mechanisms that underlie addiction-related structural changes in the brain and provides surprising insight into how these changes may actually defend the brain during excessive drug use.

Persistence of drug-seeking behaviors after long periods of abstinence has presented a major challenge for treatment of addiction. It has been hypothesized that long-term physical changes in the brain might underlie enduring behaviors associated with drug abuse. One long-lasting structural correlate that has been observed across many models of addiction is an increase in the density of dendritic spines on medium-sized spiny neurons (MSNs) in the nucleus accumbens (NAc). The spines represent critical points of communication, called excitatory synapses, between brain cells. The density of these inputs could have a major impact on the way information is processed in the brain and may regulate addiction-related behaviors.

"Although several groups have documented that repeated cocaine exposure increases NAc spine density, the precise molecular mechanisms that control this process have remained elusive," says senior study author Dr. Christopher W. Cowan from the Department of Psychiatry at The University of Texas Southwestern Medical Center. "Moreover, the cocaine-induced increase in NAc spine density has been hypothesized to contribute to the long-lasting behavioral sensitization that occurs after repeated cocaine exposure, but direct evidence concerning the functional relationship between these two processes is lacking."

Previous work demonstrated that chronic cocaine exposure increased levels of cyclin-dependent kinase 5 (Cdk5) in the NAc and that inhibition of Cdk5 blocked the cocaine-induced increase in spine density. The myocyte enhancer factor 2 (MEF2) family of transcription factors are Cdk5 targets that are expressed throughout the developing and adult brain and have been implicated in the regulation of excitatory synapses.

Dr. Cowan and colleagues found that chronic cocaine exposure reduced MEF2-dependent transcription and promoted increased MSN dendritic spine density in the NAc. Unexpectedly, expression of an overactive form of MEF2 in the NAc that blocked cocaine-induced spine density was associated with an enhanced behavioral sensitivity to cocaine whereas reduction of endogenous MEF2 proteins reduced these behaviors. These results suggest that the cocaine-induced increases in dendritic spine density may actually limit behavioral changes associated with drug addiction rather than support them.

"Taken together, our findings implicate MEF2 as a key regulator of structural synapse plasticity and sensitized responses to cocaine and suggest that reducing MEF2 activity, and thereby increasing spine density, in the NAc may be a compensatory mechanism to limit long-lasting maladaptive behavioral responses to cocaine," concludes Dr. Cowan. "A better understanding of the MEF2-associated molecular mechanisms that regulate cocaine-induced structural and behavioral plasticity could ultimately lead to the development of improved treatments for drug addiction."

Source: Cell Press

Explore further: US scientists make embryonic stem cells from adult skin

add to favorites email to friend print save as pdf

Related Stories

Egypt archaeologists find ancient writer's tomb

4 hours ago

Egypt's minister of antiquities says a team of Spanish archaeologists has discovered two tombs in the southern part of the country, one of them belonging to a writer and containing a trove of artifacts including reed pens ...

Ex-Apple chief plans mobile phone for India

4 hours ago

Former Apple chief executive John Sculley, whose marketing skills helped bring the personal computer to desktops worldwide, says he plans to launch a mobile phone in India to exploit its still largely untapped ...

NASA's space station Robonaut finally getting legs

4 hours ago

Robonaut, the first out-of-this-world humanoid, is finally getting its space legs. For three years, Robonaut has had to manage from the waist up. This new pair of legs means the experimental robot—now stuck ...

Health care site flagged in Heartbleed review

17 hours ago

People with accounts on the enrollment website for President Barack Obama's signature health care law are being told to change their passwords following an administration-wide review of the government's vulnerability to the ...

Airbnb rental site raises $450 mn

17 hours ago

Online lodging listings website Airbnb inked a $450 million funding deal with investors led by TPG, a source close to the matter said Friday.

Recommended for you

Leeches help save woman's ear after pit bull mauling

Apr 18, 2014

(HealthDay)—A pit bull attack in July 2013 left a 19-year-old woman with her left ear ripped from her head, leaving an open wound. After preserving the ear, the surgical team started with a reconnection ...

New pain relief targets discovered

Apr 17, 2014

Scientists have identified new pain relief targets that could be used to provide relief from chemotherapy-induced pain. BBSRC-funded researchers at King's College London made the discovery when researching ...

User comments : 0

More news stories

Filipino tests negative for Middle East virus

A Filipino nurse who tested positive for the Middle East virus has been found free of infection in a subsequent examination after he returned home, Philippine health officials said Saturday.

Study says we're over the hill at 24

(Medical Xpress)—It's a hard pill to swallow, but if you're over 24 years of age you've already reached your peak in terms of your cognitive motor performance, according to a new Simon Fraser University study.

NASA's space station Robonaut finally getting legs

Robonaut, the first out-of-this-world humanoid, is finally getting its space legs. For three years, Robonaut has had to manage from the waist up. This new pair of legs means the experimental robot—now stuck ...

Ex-Apple chief plans mobile phone for India

Former Apple chief executive John Sculley, whose marketing skills helped bring the personal computer to desktops worldwide, says he plans to launch a mobile phone in India to exploit its still largely untapped ...

Egypt archaeologists find ancient writer's tomb

Egypt's minister of antiquities says a team of Spanish archaeologists has discovered two tombs in the southern part of the country, one of them belonging to a writer and containing a trove of artifacts including reed pens ...

Airbnb rental site raises $450 mn

Online lodging listings website Airbnb inked a $450 million funding deal with investors led by TPG, a source close to the matter said Friday.