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Drug-seeking Circuitry In Rat Brains Identified

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In experiments with rats, researchers have identified the change in brain circuitry that drives development of a compulsion to seek drugs, even when that compulsion is self-destructive. The researchers demonstrated the function of the circuitry by selectively switching off drug-seeking in the animals. They said their findings show the key role of the brain region, known as the striatum, which is a region activated by reward.

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The researchers drew on previous studies indicating that when drug-seeking transforms from a goal-directed behavior to a compulsion, control over that behavior shifts from the ventral to dorsal region of the striatum. In their experiments, the researchers first trained rats to press a lever to obtain cocaine, which also activated a signal light. The researchers manipulated the schedule of cocaine-receiving and lever-pressing so that it would induce compulsive lever-pressing in the rats to obtain cocaine.

The researchers found that when they used surgery and drugs to sever the functional connection between the two striatal regions, the result was decreased drug-seeking behavior in rats, compared with rats in which the disconnection was not made.

In a second set of experiments, the researchers showed that the “disconnected” rats did not show reduced ability to acquire such training responses. Both normal and disconnected rats could learn to pull a chain to receive a sugar-water reward so long as the activity was continuously reinforced.

The researchers concluded that “The results of the present study demonstrate that intrastriatal connectivity is a key aspect of the functional organization of the striatum and also a critically important component of the complex neural mechanisms involved in the development of drug addiction.”

Neuron. 2008 Feb 7;57(3):432-41.
Cocaine Seeking Habits Depend upon Dopamine-Dependent Serial Connectivity Linking the Ventral with the Dorsal Striatum.
Department of Experimental Psychology, University of Cambridge, Downing Street, Cambridge CB2 3EB, UK.

A neuroanatomical principle of striatal organization has been established through which ventral domains, including the nucleus accumbens, exert control over dorsal striatal processes mediated by so-called “spiraling,” striato-nigro-striatal, circuitry. We have investigated the functional significance of this circuitry in the control over a cocaine-seeking habit by using an intrastriatal disconnection procedure that combined a selective, unilateral lesion of the nucleus accumbens core and infusion of a dopamine receptor antagonist into the contralateral dorsolateral striatum, thereby disrupting striato-midbrain-striatal serial connectivity bilaterally. We show that this disconnection selectively decreased drug-seeking behavior in rats extensively trained under a second-order schedule of cocaine reinforcement. These data thereby define the importance of interactions between ventral and dorsal domains of the striatum, mediated by dopaminergic transmission, in the neural mechanisms underlying the development and performance of cocaine-seeking habits that are a key characteristic of drug addiction.

 see also

Subconscious Signals Can Trigger Drug Craving

 

Written by huehueteotl

February 8, 2008 at 4:20 pm

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