New clue to cocaine addicts' quirky behavior

Researchers working with rats have zeroed in on the brain circuitry mechanism whose disruption contributes to the impulsive behavior seen in users of cocaine as well as other psychostimulant drugs. The same circuitry has been implicated in such disorders as schizophrenia, depression, and post-traumatic stress disorder, wrote the researchers.

Yukiori Goto and Anthony A. Grace of the University of Pittsburgh described their findings in the July 21, 2005, issue of Neuron. In their studies, they sought to understand the effects of cocaine sensitization on the connections between two higher brain regions--the prefrontal cortex and the hippocampus--and the nucleus accumbens, which is the region in the limbic system involved in processing reward behavior. The prefrontal cortex is involved in processing information, and the hippocampus is involved in learning and memory.

The connections to the nucleus accumbens seem to be bidirectional, said the researchers, and the interactions with the prefrontal cortex and hippocampus could affect the "plasticity" of connections in the neurons of the nucleus accumbens. This means that disruptions to the normal connections could affect behavior.

The researchers' electrophysiological studies of the effects of cocaine on this circuitry demonstrated that the drug did disrupt this normal plasticity. They found that the cocaine induced abnormal enhancement of neuronal connections--a phenomenon called long-term potentiation (LTP).

The researchers also performed behavioral studies on the cocaine-sensitized rats, to explore the behavioral effects of this disruption. In these studies, they placed the rats in a plus-shaped maze. The rats were taught that in response to a visual cue they should turn left or right toward one arm or the other of the maze to obtain a piece of cereal.

Goto and Grace found that, while the cocaine-sensitized rats learned the correct response strategy faster than normal rats, they were significantly less able to change strategies when they were required to ignore the cue and always make a left or right turn to receive the reward.

"Thus, although abnormally induced LTP by psychostimulants at limbic inputs might not interfere with learning a response strategy, it may reduce the capacity of these animals to consider alternate response strategies," concluded Goto and Grace. "In this way, the disruption of synaptic plasticity by cocaine sensitization may contribute to the affective- and context-inappropriate impulsive behaviors that are characteristic of drug addiction."

This work was supported by USPHS and National Alliance for Research on Schizophrenia and Depression Young Investigator Award. Y.G. is NARSAD Essel Investigator.

Goto and Grace: "Dopamine-dependent Interactions between Limbic and Prefrontal Cortical Plasticity in the Nucleus Accumbens: Disruption by Cocaine Sensitization" Publishing in Neuron, Vol. 47, July 21, 2005, pages 255–266. DOI 10.1016/j.neuron.2005.06.017. www.neuron.org

Source : Cell Press