Chronic unilateral stimulation of the nucleus accumbens at high or low frequencies attenuates relapse to cocaine seeking in an animal model.

Abstract

Deep brain stimulation (DBS), a form of neurosurgical intervention that is used to modulate the electrophysiological activity of specific brain areas, has emerged as a form of therapy for severe cases of treatment-refractory addiction. Recent research suggests that the nucleus accumbens (NAC) is a promising target area for DBS in addiction. The current experiments were designed to determine optimal parameters of stimulation and long-term efficacy of NAC DBS in an animal model of cocaine addiction. Rats were implanted with a stimulating electrode in the right NAC and exposed to chronic cocaine self-administration (0.5mg/kg/infusion). Rats underwent drug seeking tests by exposing them to the self-administration context paired with cocaine challenge (5mg/kg i.p.) on days 1, 15 and 30 after withdrawal from cocaine self-administration. Low-frequency (LF, 20Hz) or high-frequency (HF, 160Hz) DBS was applied for 30min daily for 14 consecutive days starting one day after drug withdrawal. Rats exhibited robust drug-seeking 1, 15 and 30 days after withdrawal from cocaine self-administration, with responding being highest on day 15. Both LF and HF attenuated cocaine seeking on day 15 post-withdrawal by 36 and 48%, respectively. Both forms of stimulation were ineffective on the tests conducted on days 1 and 30. The present data showed that unilateral DBS of the NAC effectively attenuated cocaine relapse after 15 days of drug withdrawal, with therapeutic-like effects seemingly diminishing after DBS discontinuation. This evidence provides support for DBS as a promising intervention in intractable cases of stimulant addiction.