Nucleus accumbens core and pathogenesis of compulsive checking

Abstract

To investigate the role of the nucleus accumbens core (NAc) in the development of quinpirole-induced compulsive checking, rats received an excitotoxic lesion of NAc or sham lesion and were injected with quinpirole (0.5 mg/kg) or saline; development of checking behavior was monitored for 10 biweekly tests. The results showed that even after the NAc lesion, quinpirole still induced compulsive checking, suggesting that the pathogenic effects produced by quinpirole lie outside the NAc. Although the NAc lesion did not prevent the induction of compulsive checking, it altered how quickly it develops, suggesting that the NAc normally contributes toward the induction of compulsive checking. Saline-treated rats with an NAc lesion were hyperactive, but did not develop compulsive checking, indicating that hyperactivity by itself is not sufficient for the pathogenesis of compulsive checking. It is proposed that compulsive checking is the exaggerated output of a security motivation system and that the NAc serves as a neural hub for coordinating the orderly activity of neural modules of this motivational system. Evidence is considered suggesting that the neurobiological condition for the pathogenesis of compulsive checking is two-fold: activation of dopamine D2/D3 receptors without concurrent stimulation of D1-like receptors and long-term plastic changes related to quinpirole-induced sensitization.

Supersensitive Kappa Opioid Receptors Promotes Ethanol Withdrawal-Related Behaviors and Reduce Dopamine Signaling in the Nucleus Accumbens

“…Human alcoholics report relapse to alcohol drinking in an effort to reduce withdrawal symptoms experienced during abstinence ( Wetterling et al, 2006 ). As mounting evidence supports the involvement of accumbal KORs in the development of anxiety/compulsive-like behaviors and dependence-induced ethanol drinking ( Nealey et al, 2011 ; Ballester-Gonzáles et al, 2015 ), chronic ethanol-induced reductions in dopamine transmission and increased KOR sensitivity in the NAc may promote the development of negative affective behavioral phenotypes associated with ethanol withdrawal. As such, our work supports a growing body of literature suggesting the potential utility of a KOR-antagonist to rescue chronic ethanol-induced changes in behavior and neurobiology.…”

“…The time-course of these findings is similar to CIE-induced increases in ethanol drinking using a similar protocol ( Griffin et al, 2009 ), suggesting a link between attenuated accumbal function and augmented ethanol intake. As the dopamine system has been implicated as an important regulator of ethanol drinking ( Nealey et al, 2011 ) and anxiety/compulsive-like behaviors ( Ballester-Gonzáles et al, 2015 ), it is possible that dysregulated dopamine transmission may underlie chronic ethanol-induced increases in these behaviors.…”

Validity of Quinpirole Sensitization Rat Model of OCD: Linking Evidence from Animal and Clinical Studies

“…Notably, a recent study showed that lesion of the NAc did not prevent the development of compulsive checking in the QSM. It only reduced the speed in which checking developed (Ballester González et al, 2015). Interestingly, a recent human DBS study in OCD patients showed that NAc-DBS reduced low-frequency EEG oscillations recorded over the frontal cortex during symptom provocation as well as resting-state functional connectivity (fMRI) between NAc and the prefrontal cortex (Figee et al, 2013a).…”

Role of the medial prefrontal cortex and nucleus accumbens in an operant model of checking behaviour and uncertainty

“…This quinpirole-induced checking is comparable with findings from a well-established open-field model of checking in rodents ( Szechtman et al, 1998 ), in which excessive returns to a ‘home base’ in the open-field are interpreted as ‘checking behaviour’. Evidence from open-field checking also clearly implicates the NAc core in control of the vigour or extent of checking ( Ballester González et al, 2015 ; Dvorkin et al, 2010 ). NAc core lesions increased ‘checking’ to an extent comparable with checking in unlesioned, quinpirole-treated rats ( Dvorkin et al, 2010 ) and delayed, but did not prevent, the development of checking ( Ballester González et al., 2015 ).…”

“…Evidence from open-field checking also clearly implicates the NAc core in control of the vigour or extent of checking ( Ballester González et al, 2015 ; Dvorkin et al, 2010 ). NAc core lesions increased ‘checking’ to an extent comparable with checking in unlesioned, quinpirole-treated rats ( Dvorkin et al, 2010 ) and delayed, but did not prevent, the development of checking ( Ballester González et al., 2015 ). Cortical input into the neural circuitry of checking is less clear; in contrast with NAc lesions, orbitofrontal cortex (OFC) lesions did not directly increase checking but produced changes in goal-directed activity in the open-field checking task.…”