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

Abstract

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 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.

Deep brain stimulation of the nucleus accumbens core but not shell reduces motivational components of heroin taking and seeking in rats

“…A possible explanation is that only repeated or long-term NAcore DBS is effective in decreasing heroin priming-induced reinstatement as opposed to a single 1-h stimulation. In fact, long-term NAshell DBS seems to be effective in reducing morphine seeking (Ma et al, 2013) and alcohol taking (Wilden et al, 2014), contradicting the null effects of acute NAshell DBS in this study.…”

A General Method for Evaluating Deep Brain Stimulation Effects on Intravenous Methamphetamine Self-Administration

“…The nucleus accumbens shell was targeted given its known involvement in drug-consummatory behavior 8 using the following stereotactic coordinates relative to bregma (AP + 1.6, DV -8.5, ML ± 2.4). Stimulation parameters and duration were loosely based on previous published experience with DBS for the treatment of psychiatric disease 8,20,21 but can be adjusted depending on the experimenter's needs. Error bars are moderate and not all days reach significance indicating the range of responses that can be seen in behavioral assessments despite a clear treatment effect.…”

“…Typical parameters for high frequency stimulation in rats are similar to those used in clinical human deep brain stimulation: frequency of 130 to180 Hz, pulse width of 60 to 90 msec, and current amplitude of 100 to 250 μA 4,[8][9][10] . Note: A lower current is used in the rodent due to its reduced size compared to the primate.…”

“…Deep brain stimulation (DBS) is a neurosurgical procedure that uses a brain "pacemaker" to normalize disruptive neuronal firing patterns that occur in certain diseases, including Parkinson's disease, dystonia, and essential tremor 3 . Recent human case reports suggest that DBS may also be an effective treatment for alcohol and drug dependence, but preclinical evidence regarding psychostimulants (e.g., cocaine, methamphetamine) is limited [4][5][6][7][8] .…”

La chirurgie au secours des addictions

“…La stimulation profonde de la partie dorsomédiane (shell), comme son inactivation pharmacologique, réduisent également la préférence et la consommation d'alcool [20,21]. Elle peut aussi réduire le comportement de recherche de cocaïne sans affecter la recherche de nourriture [22,23].…”