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

Abstract

Background: Deep brain stimulation is explored as a new intervention for treatment-resistant substance use dependence. A candidate brain region is the nucleus accumbens, due to its involvement in reward and motivation. This study aimed to explore effects of NAcore and NAshell deep brain stimulation on aspects of heroin taking and seeking in a self-administration model for rats. Methods: NAcore and NAshell deep brain stimulation was applied during 25 or 100 µg/kg/infusion heroin self-administration on an FR4 schedule of reinforcement and during cue-and heroin-induced reinstatement. In a separate group, effects of NAcore deep brain stimulation on heroin selfadministration on a progressive ratio schedule and the first extinction session were examined. Results: NAcore and NAshell deep brain stimulation did not alter heroin self-administration on an FR4 schedule. NAcore deep brain stimulation decreased cue -but not drug-induced reinstatement of heroin seeking, whereas NAshell deep brain stimulation did not affect reinstatement responding. In the second experiment, NAcore deep brain stimulation reduced responding during a progressive ratio schedule of heroin reinforcement. Finally, deep brain stimulation facilitated extinction from day 1 throughout the course of extinction learning. Conclusion: Taken together, the differential effects of NAcore and NAshell deep brain stimulation on heroin taking and seeking are in line with the distinct functional roles of these sub-regions therein. Conditioned cues have been shown to be very powerful stimuli for the persistence of addiction and relapse to drug use. Therefore, the present findings that NAcore deep brain stimulation decreases motivation for heroin taking and cue-conditioned behaviour and facilitates extinction learning are very promising, supporting the positive findings from clinical case studies.

High frequency deep brain stimulation can mitigate the acute effects of cocaine administration on tonic dopamine levels in the rat nucleus accumbens

“…Both the NAcc ( Liu et al, 2008 ; Knapp et al, 2009 ; Guo et al, 2013 ; Schippers et al, 2017 ) and shell ( Knapp et al, 2009 ; Henderson et al, 2010 ; Ma et al, 2013 ; Batra et al, 2017 ) have been shown to be promising DBS targets for SUD for substances such as morphine, alcohol, heroin, and methamphetamine. The underlying treatment mechanism has not been fully understood.…”

“…NAc DBS has shown promising results for the treatment of SUD ( Liu et al, 2008 ; Knapp et al, 2009 ; Henderson et al, 2010 ; Guo et al, 2013 ; Ma et al, 2013 ; Batra et al, 2017 ; Schippers et al, 2017 ; Yuen et al, 2022b ). Here we hypothesized that the therapeutic effects of NAc DBS may be due to its ability to rapidly modulate tonic dopamine concentrations.…”

Deep brain stimulation of the nucleus accumbens shell attenuates cocaine withdrawal but increases cocaine self-administration, cocaine-induced locomotor activity, and GluR1/GluA1 in the central nucleus of the amygdala in male cocaine-dependent rats

“…One way to address this issue would be to use a progressive ratio schedule of reinforcement. Future studies should also determine the effect of single vs multipe cycles of DBS on models of relapse such as cue-, stress-, and drug-induced relapse [18,21,48,49,78]). High-frequency DBS of the NAcc shell also produced an increase in cocaine-induced locomotor activity that we interpret as a decrease in tolerance to the psychostimulant effects of cocaine and a decrease in irritability-like behavior that we interpret as a decrease in negative emotional states.…”