Deep Brain Stimulation of the Nucleus Accumbens Shell Attenuates Cocaine Reinstatement through Local and Antidromic Activation

Abstract

Accumbal deep brain stimulation (DBS) is a promising therapeutic modality for the treatment of addiction. Here, we demonstrate that DBS in the nucleus accumbens shell, but not the core, attenuates cocaine priming-induced reinstatement of drug seeking, an animal model of relapse, in male Sprague Dawley rats. Next, we compared DBS of the shell with pharmacological inactivation. Results indicated that inactivation using reagents that influenced (lidocaine) or spared (GABA receptor agonists) fibers of passage blocked cocaine reinstatement when administered into the core but not the shell. It seems unlikely, therefore, that intrashell DBS influences cocaine reinstatement by inactivating this nucleus or the fibers coursing through it. To examine potential circuit-wide changes, c-Fos immunohistochemistry was used to examine neuronal activation following DBS of the nucleus accumbens shell. Intrashell DBS increased c-Fos induction at the site of stimulation as well as in the infralimbic cortex, but had no effect on the dorsal striatum, prelimbic cortex, or ventral pallidum. Recent evidence indicates that accumbens DBS antidromically stimulates axon terminals, which ultimately activates GABAergic interneurons in cortical areas that send afferents to the shell. To test this hypothesis, GABA receptor agonists (baclofen/ muscimol) were microinjected into the anterior cingulate, and prelimbic or infralimbic cortices before cocaine reinstatement. Pharmacological inactivation of all three medial prefrontal cortical subregions attenuated the reinstatement of cocaine seeking. These results are consistent with DBS of the accumbens shell attenuating cocaine reinstatement via local activation and/or activation of GABAergic interneurons in the medial prefrontal cortex via antidromic stimulation of cortico-accumbal afferents.

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

“…However, the results contrast those of Vassoler et al (2013) who report that NAshell but not NAcore DBS attenuates cocaineprimed reinstatement. This discrepancy could be explained by the involvement of partly distinct circuits thought to be involved in cocaine and opioid dependence (Badiani et al, 2011).…”

The application of deep brain stimulation in the treatment of psychiatric disorders

“…Some DBS animal models suggest that attenuation of addictive behaviours depends on modulation of the NAc shell (Vassoler et al, 2013;Wilden et al, 2014), which is the part of the NAc that regulates reward perception and the hedonic effects of drugs. Addiction symptoms increase and decrease over time, and vulnerability for drug taking may last only a few hours or days and is influenced by anxiety, stress, or environmental factors.…”

Nucleus Accumbens and Posterior Amygdala Mediate Cue-Triggered Alcohol Seeking and Suppress Behavior During the Omission of Alcohol-Predictive Cues

“…Conversely, increases in basal firing of medial Acb neurons are associated with inhibition of lever pressing during a reward omission cue and ambulation away from a drug-paired chamber (German and Fields, 2007;Ghazizadeh et al, 2012). Finally, AcbSh electrical or deep brain stimulation inhibits reward-associated behaviors including sucrose licking and cocaine-primed reinstatement (Krause et al, 2010;Vassoler et al, 2013). However, AcbSh is also necessary for the performance of several reward-reinforced behaviors; AcbSh lesions or inactivations disrupt the potentiating effect of Pavlovian conditioned cues on instrumental behavior (Corbit et al, 2001), conditioned approach during a sucrose-reinforced cue (Blaiss and Janak, 2009), and context-induced reinstatement of drug seeking (Cruz et al, 2014).…”