Deep brain stimulation of the nucleus accumbens reduces alcohol intake in alcohol-preferring rats

摘要

Object The authors tested the hypothesis that deep brain stimulation (DBS) in the nucleus accumbens (NAcc) decreases alcohol intake in alcohol-preferring (P) rats after each animal has established a stable, large alcohol intake and after P rats with an established intake have been deprived of alcohol for 4–6 weeks. Methods Bipolar stimulating electrodes were bilaterally placed in the NAcc using stereotactic coordinates. In the first study, P rats (9 animals) were allowed to establish a stable pattern of alcohol intake (about 5–7 g/day) over approximately 2 weeks, and the acute effects of DBS in the NAcc (140–150 Hz, 60-μsec pulse width, and 200-μA current intensity) on alcohol intake and alcohol preference were studied. Each animal acted as its own control and received 1 hour of DBS followed by 1 hour of sham-DBS or vice versa on each of 2 sequential days. The order of testing (sham-DBS vs DBS) was randomized. In the second study, each animal was allowed to establish a stable alcohol intake and then the animal was deprived of alcohol for 4–6 weeks. Animals received DBS (6 rats) or sham-DBS (5 rats) in the NAcc for 24 hours starting when alcohol was reintroduced to each animal. Results Deep brain stimulation in the NAcc, as compared with a period of sham-DBS treatment in the same animals, acutely decreased alcohol preference. Furthermore, alcohol consumption and preference were significantly reduced in the DBS group compared with the sham treatment group during the first 24 hours that alcohol was made available after a period of forced abstinence. Conclusions The NAcc plays a key role in the rewarding and subsequent addictive properties of drugs of abuse in general and of alcohol in particular. Deep brain stimulation in the NAcc reduced alcohol consumption in P rats both acutely and after a period of alcohol deprivation. Therefore, DBS in the NAcc coupled with other neurophysiological measurements may be a useful tool in determining the role of the NAcc in the mesocorticolimbic reward circuit. Deep brain stimulation in the NAcc may also be an effective treatment for reducing alcohol consumption in patients who abuse alcohol and have not responded to other forms of therapy.