Reduced ethanol consumption by alcohol-preferring (P) rats following pharmacological silencing and deep brain stimulation of the nucleus accumbens shell.
OBJECTIVE
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 γ-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 EtOH 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 μA (3-4 rats/group) of DBS to examine the effect on daily consumption of oral EtOH 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 EtOH consumption by 55% in chronically drinking rats. Similarly, in the second experiment, 200 μA 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 EtOH 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.
Department of Neurosurgery, Louisiana State University Health Sciences Center, Shreveport, Louisiana;
Jessica A
JA
Wilden
Kurt Y
KY
Qing
Sheketha R
SR
Hauser
William J
WJ
McBride
Pedro P
PP
Irazoqui
Zachary A
ZA
Rodd
D000428:Alcohol Drinking / Q000503:physiopathology / Q000628:therapy*; D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D003216:Conditioning, Operant / Q000187:drug effects / Q000502:physiology; D046690:Deep Brain Stimulation; D000431:Ethanol / Q000008:administration & dosage*; D005260:Female; D018755:GABA Agonists / Q000494:pharmacology; D009118:Muscimol / Q000494:pharmacology; D009714:Nucleus Accumbens / Q000187:drug effects / Q000503:physiopathology*; D051381:Rats; D012201:Reward; D012646:Self Administration
D018755:GABA Agonists; D009118:Muscimol; D000431:Ethanol; D001418:Baclofen