Reduced ethanol consumption by alcohol-preferring (P) rats following pharmacological silencing and deep brain stimulation of the nucleus accumbens shell

Object. There is increasing interest in deep brain stimulation (DBS) for the treatment of addiction. Initial testing must be conducted in animals, and the alcohol-preferring (P) rat meets the criteria for an animal model of alcoholism. This study is composed of 2 experiments designed to examine the effects of 1) pharmacological inactivation and 2) DBS of the nucleus accumbens shell (AcbSh) on the consumption of alcohol by P rats. Methods. In the first experiment, the effects of reversible inactivation of the AcbSh were investigated by administering intracranial injections of gamma-aminobutyric acid (GABA) agonists. Bilateral microinjections of drug were administered to the AcbSh in P rats (8-10 rats/group), after which the animals were placed in operant chambers containing 2 levers one used to administer water and the other to administer 15% EtOH to examine the acquisition and maintenance of oral Et0H self-administration. In the second experiment, a DBS electrode was placed in each P rat's left AcbSh. The animals then received 100 or 200 mu A (3-4 rats/group) of DBS to examine the effect on daily consumption of oral Et0H in a free-access paradigm. Results. In the first experiment, pharmacological silencing of the AcbSh with GABA agonists did not decrease the acquisition of EtOH drinking behavior but did reduce Et0H consumption by 55% in chronically drinking rats. Similarly, in the second experiment, 200 RA of DBS consistently reduced EtOH intake by 47% in chronically drinking rats. The amount of EtOH consumption returned to baseline levels following termination of therapy in both experiments. Conclusions. Pharmacological silencing and DBS of the AcbSh reduced Et0H intake after chronic EtOH use had been established in rodents. The AcbSh is a neuroanatomical substrate for the reinforcing effects of alcohol and may be a target for surgical intervention in cases of alcoholism.