Abstract
The anterior insular cortex (AIC) has been implicated in addictive behaviour, including the loss of control over drug intake, craving and the propensity to relapse. Evidence suggests that the influence of the AIC on drug-related behaviours is complex as in rats exposed to extended access to cocaine self-administration, the AIC was shown to exert a state-dependent, bidirectional influence on the development and expression of loss of control over drug intake, facilitating the latter but impairing the former. However, it is unclear whether this influence of the AIC is confined to stimulant drugs that have marked peripheral sympathomimetic and anxiogenic effects or whether it extends to other addictive drugs, such as opiates, that lack overt acute aversive peripheral effects. We investigated in outbred rats the effects of bilateral excitotoxic lesions of AIC induced both prior to or after long-term exposure to extended access heroin self-administration, on the development and maintenance of escalated heroin intake and the subsequent vulnerability to relapse following abstinence. Compared to sham surgeries, pre-exposure AIC lesions had no effect on the development of loss of control over heroin intake, but lesions made after a history of escalated heroin intake potentiated escalation and also enhanced responding at relapse. These data show that the AIC inhibits or limits the loss of control over heroin intake and propensity to relapse, in marked contrast to its influence on the loss of control over cocaine intake.
Highlights
The anterior insular cortex (AIC) has been increasingly implicated in the pathophysiology, and associated behavioural manifestations of, drug addiction (Naqvi & Bechara, 2009; Verdejo-Garcia et al, 2012)
The results of the present study show that pre-exposure bilateral excitotoxic lesions of the AIC have no effect on the acquisition of heroin SA or the establishment of the escalation of heroin intake that develops over 19 days of extended access
Rats with post-training AIC lesions, made once they have reached a plateau of escalated intake (Ahmed et al, 2000; McNamara et al, 2010) that usually remains stable for weeks (McNamara et al, 2010), continued to escalate their intake whereas sham-operated control rats maintained the pre-lesion plateau
Summary
The anterior insular cortex (AIC) has been increasingly implicated in the pathophysiology, and associated behavioural manifestations of, drug addiction (Naqvi & Bechara, 2009; Verdejo-Garcia et al, 2012). The behavioural consequences of damage to the insula in humans drug addiction have been suggested to reflect the role of this structure in interoception (Craig, 2003; Craig, 2009; Craig, 2011; Paulus & Stewart, 2014; Stewart et al, 2019) and its associated influence on emotions (Craig, 2004; Wiens, 2005; Verdejo-Garcia et al, 2006; Craig, 2010) and executive functions (Engstrom et al, 2014), such as impulse control and decision-making (Weller et al, 2009; Naqvi & Bechara, 2010; Jones et al, 2011; Pattij et al, 2014; Herman et al, 2018; Rae et al, 2019). A high impulsivity trait in humans (Lopez-Larson et al, 2012) and rats (Belin-Rauscent et al, 2015) is associated with decreased thickness of the AIC, and has been shown across species to confer an increased tendency to escalate cocaine (Dalley et al, 2007), but not heroin (McNamara et al, 2010) intake and a vulnerability to switch from controlled to compulsive cocaine SA (Belin et al, 2008; Ersche et al, 2012)
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