Deep brain stimulation of the nucleus accumbens reduces ethanol consumption in rats

Abstract

Recent studies have shown that deep brain stimulation (DBS) of the nucleus accumbens (NAcc) has an inhibitory effect on drug-seeking behaviors including reinstatement responding for cocaine. The objective of the present study was to expand on these findings by assessing the effects of DBS on behaviors related to alcohol consumption. The specific aim of this study was to determine whether DBS delivered to either the shell or core of the NAcc would reduce ETOH intake in rats using a two-bottle choice limited access procedure. Long Evans rats were induced to drink a 10% ethanol solution using a saccharin fading procedure. Bipolar electrodes were implanted bilaterally into either the core or shell of the NAcc. During testing animals received DBS 5 min prior to and during a 30-minute test session in which both ETOH and water bottles were accessible. Current was delivered at amplitudes ranging from 0 to 150 µA. ETOH consumption was significantly reduced from baseline levels at the 150 µA current for both shell and core electrode placements. A significant current effect was not found for water consumption for either site. These results provide evidence that DBS delivered either to the nucleus accumbens core or shell subregions can significantly reduce ethanol intake in the rat.

Introduction

Deep brain stimulation (DBS) involves the continuous electrical low intensity stimulation of select brain areas. DBS has been found to have a number of therapeutic applications including the treatment of movement disorders such as Parkinson's disease (Krack et al., 2003) and of psychiatric disorders that include depression (Lozano et al., 2008) and obsessive compulsive disorder (Greenberg et al., 2008). A few recent preclinical studies have focused on the effects of deep brain stimulation in models of substance abuse disorders. With respect to psychomotor stimulants, delivery of deep brain stimulation over a two hour long test session to the shell of the nucleus accumbens has been found to selectively block reinstatement responding for cocaine induced by the priming dose of this psychomotor stimulant (Vassoler et al., 2008). Morphine-induced conditioned place preference has been reported to be attenuated by the delivery of deep brain stimulation to the nucleus accumbens core during the conditioning phase (Liu et al., 2008). This finding suggests that DBS delivered to the core of the accumbens may either alter the rewarding effects of opioids or may otherwise disrupt other mechanisms involved in the acquisition of opioid-related conditioned responses.

Stimulation of the nucleus accumbens was associated with decreased ethanol consumption by an alcohol dependent patient (Kuhn et al., 2007). Other than this single case study there appear to be no other published reports concerning the effects of DBS on alcohol consumption. The finding that stimulation of the nucleus accumbens may produce this effect is consistent with evidence that this structure may play a role in regulating ethanol consumption behaviors. Other evidence that implicates the nucleus accumbens in regulating the processes associated with ethanol consumption includes findings that spike activity in this structure is altered during operant responding for alcohol (Janak et al., 1999). Also energy metabolism is increased in the shell of the accumbens of rats while they are drinking ethanol (Porrino et al., 1998a, Porrino et al., 1998b). Pharmacological manipulations such as the injection of the GABA_A receptor agonist muscimol (Hodge et al., 1995) or the dopamine receptor antagonist fluphenazine (Rassnick et al., 1992) into the nucleus accumbens have an inhibitory effect on responding for ethanol. During periods of alcohol consumption dopamine levels in the accumbens may be increased (Doyon et al., 2003). Some results do suggest, however, that dopamine within the nucleus accumbens regulates ethanol seeking but not consummatory behaviors (Ikemoto et al., 1997, Samson and Chappell, 2004).

The objective of the present study was to assess whether DBS delivered to the nucleus accumbens would alter ethanol consumption by rats given limited access to 10% alcohol–water solutions. A second bottle containing water was also made available to animals during test sessions to assess whether DBS had any effect on the small amounts of water that rats consumed during these sessions.

The nucleus accumbens has core and shell subregions that have somewhat distinct projection patterns (Heimer et al., 1991). These subregions also differ with respect to relative distribution of certain neuropeptides such as cholecystokinin (Lança et al., 1998) and in the density of some receptor populations including high affinity neurotensin receptors (Pickel et al., 2001). The differences between these two subregions may have functional significance with regard to their response to the presence of ethanol. For example, dopamine release produced by the acute administration of ethanol may be more pronounced in the shell than in the core of the accumbens (Howard et al., 2008) and chronic ethanol treatment results in greater expression of the transcription factor ΔFosB in the core as compared to the accumbens shell (Perrotti et al., 2008). Because of possible differences in the role played by the accumbens core and shell in regulating ethanol consumption separate core and shell targeted groups of animals were tested in the present study.