Enhancing the function of certain glutamate neurotransmitter receptors in the brains of rats experiencing cocaine withdrawal can suppress drug seeking behavior according to a study published online this week in Nature Neuroscience. These findings suggest a potential pharmacological therapeutic strategy for the prevention of relapse in addiction.
When recovering addicts are in a situation that reminds them of prior drug use, they often experience cravings, which can precipitate relapse. Withdrawal-induced craving is tied to molecular changes in the nucleus accumbens, a brain region known to participate in addiction processes. Previous studies have reported that in rats Wolf and colleagues had previously shown that cocaine use followed by prolonged withdrawal led to a long-lasting increase in neuronal synaptic transmission, mediated by calcium-permeable AMPA receptors (CP-AMPAR) in the nucleus accumbens. Also, CP-AMPAR-mediated synaptic transmission can be suppressed by the activation of a glutamate receptor called mGluR1.
Marina Wolf and colleagues tested the effect of SYN119, a molecule that can enhance mGluR1 function, on cravings in rats. They found that rats having undergone cocaine withdrawal and exposed to cues previously associated with cocaine consumption showed reduced craving when SYN119 was administered. In addition, the mGluR1 enhancer normalized the level of CP-AMPAR-mediated synaptic transmission in the nucleus accumbens of these animals.
While it is not known whether these results will translate to human addicts, they provide a new lead for the development of therapeutics designed to control relapse. The effects of SYN119 lasted several days, suggesting that mGluR1 enhancer treatment could represent a viable option to prolong abstinence in former addicts.
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