Dysregulation of the
nociceptin (N/OFQ) system has been implicated in
alcohol abuse and
alcoholism, and growing evidence suggests that targeting this system may be beneficial for treating
alcoholism. To further explore the treatment target potential of the N/OFQ system, the novel non-
peptide, small-molecule N/OFQ (NOP) agonist
MT-7716, (R)-
2-{3-[1-(Acenaphthen-1-yl)piperidin-4-yl]-2-oxo-2,3-dihydro-1H-benzimidazol-1-yl}-N-methylacetamide hydrochloride hydrate, was examined for its effects on
ethanol self-administration and stress-induced reinstatement of alcohol seeking in non-dependent and post-dependent rats. Male Wistar rats were trained to self-administer
ethanol and then made
ethanol dependent via repeated intragastric
ethanol intubation. The effects of
MT-7716 (0.3 and 1 mg/kg; PO) on alcohol
self-administration were determined 2 weeks following dependence induction, when baseline
self-administration was restored. Effects of
MT-7716 on stress-induced reinstatement were tested in separate cohorts of rats, 1 and 3 weeks post-withdrawal.
MT-7716 reduced alcohol
self-administration and stress-induced reinstatement of alcohol seeking in post-dependent rats, but was ineffective in non-dependent animals. Moreover, the prevention of stress-induced reinstatement by
MT-7716 was more pronounced at 3 weeks post-dependence. The results further confirm treatment target potential for the NOP receptor and identify non-
peptide NOP agonists as promising potential treatment drugs for
alcohol abuse and
relapse prevention. The findings also support dysregulation of the N/OFQ system as
a factor in alcohol seeking and reinforcement.