November 4, 2016

Probing drug abuse circuitry

Vanderbilt researchers have identified cocaine-induced modifications at specific neuronal connections, which could aid the development of new therapies for substance abuse disorders.

(iStock)
(iStock)

Understanding how drugs of abuse affect the brain’s neuronal connections is vital to developing treatments for substance abuse disorders. Previous studies have demonstrated that changes in a brain region called the nucleus accumbens underlie behavioral responses to cocaine and susceptibility to relapse.

Max Joffe, Ph.D., and Brad Grueter, Ph.D., used a light-based technology called optogenetics to study how cocaine alters the activity of inputs to the nucleus accumbens from specific brain regions.

They found that cocaine experience in mice confers distinct modifications of excitatory inputs from the midline nuclei of the thalamus (mThal) and from the prefrontal cortex to the nucleus accumbens. They demonstrated enhanced function – and altered subunit composition – of excitatory NMDA receptors at mThal-nucleus accumbens synapses.

The findings, reported in the Nov. 1 issue of Biological Psychiatry, identify cocaine-induced modifications at synapses in the nucleus accumbens and suggest that modified NMDA receptors may be a therapeutic target for psychostimulant use disorders.

This research was supported by the National Institutes of Health (grant DA031699).

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