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Synergistic therapies may prevent drug relapse

Silencing specific brain circuits unleashes the robust and sustained anti-relapse potential of environmental enrichment, a study suggests.

Environmental enrichment promotes brain development and recovery through exposure to stimulating physical surroundings. Prior exposure to stimulating environments can also reduce drug-seeking behavior in animals, but when applied after drug exposure, environmental enrichment results in only a small, temporary reduction in drug craving.

Yan Dong and colleagues examined whether the therapeutic effects of environmental enrichment could be enhanced and prolonged by remodeling neural projections from the basolateral amygdala (BLA) to the nucleus accumbens (NAc) – a brain circuit that mediates drug craving.

The authors allowed rats to insert their noses into a hole to self-administer cocaine for 6 days. Forty-five days later, some of the rats underwent an optogenetic procedure that specifically weakened the BLA-to-NAc projection by inducing a cellular process called long-term depression (LTD). During the following week, the rats were housed in environmental enrichment cages consisting of toys, tunnels of different shapes, and running wheels.

The combined treatment of environmental enrichment and LTD-induced silencing of BLA-to-NAc synapses led to persistent anti-relapse effects, resulting in fewer nose insertions 3 weeks later, compared with environmental enrichment alone. According to the authors, the findings highlight the potential of using synergistic behavioral and circuit-specific approaches to treat drug addiction.

Article #15-24739: “Re-silencing of silent synapses unmasks anti-relapse effects of environmental enrichment,” by Yao-ying Ma et al. To be published in PNAS the week of April 18.