KAPPA OPIOID RECEPTOR BLOCKADE IN NAc SHELL PREVENTS SEX-DEPENDENT
ALCOHOL RELAPSE-LIKE BEHAVIOUR INDUCED BY INFLAMMATORY PAIN.
Background and Purpose Pain-induced negative affect reduces life quality
of patients by increasing psychiatric comorbidities, including alcohol
use disorders (AUD). Indeed, clinical data suggest pain as a risk factor
to suffer AUD, predicting relapse drinking in abstinent patients. Here,
we analyse the impact of pain on alcohol relapse and the role of kappa
opioid receptors (KOR) activation in mediating this pain-induced effects
since KOR play an important role in pain-driven negative affect and AUD.
Experimental approach Female and male Sprague Dawley rats underwent to
two alcohol intermittent access periods separated by a forced abstinence
period. The complete Freund adjuvant (CFA) model of inflammatory pain
was introduced during abstinence and alcohol intake after alcohol
reintroduction was assessed. Additionally, we used behavioural
approaches to measure stress and memory impairment and biochemical
assays to measure KOR expression in abstinence and reintroduction
periods. Finally, KOR antagonist norbinaltorphimine (norBNI) was
administered in the nucleus accumbens shell (NAcS) during abstinence to
prevent pain-induced alcohol relapse-like phenomenon in CFA-female rats.
Key results Only female CFA-treated rats increased alcohol intake during
reintroduction period. Concomitantly, this group showed enhanced
stress-like behaviour and increased KOR expression in the NAcS that was
developed during abstinence and remained during reintroduction period.
Finally, norBNI administered in the NAcS prevented pain-induced alcohol
relapse-like behaviour in female rats. Conclusions and implications Our
data evidenced that inflammatory pain constitutes a risk factor to
relapse only in female rats, by the arise and maintenance of stress
probably mediated by kappa opioid receptor (KOR) signaling in the NAcS.