Oprl1, encoding the nociceptin/orphanin FQ receptor (NOP), is a key regulator in multiple biological processes. The NOP receptor is involved in the nociceptin/Orphanin FQ (N/OFQ) system, which has a significant impact on hippocampal function, learning, memory, and emotional regulation [1,6]. It is also associated with the regulation of pain, reward, and stress-related responses [3,4,5].

In a mouse model combining adverse maternal environment (AME) and post-weaning Western diet (WD), an AME and an AME-WD significantly increased the total hippocampal expression of Oprl1 and variant V4 in male offspring, through an epigenetic mechanism. This altered expression may contribute to cognitive impairment in adult males [1]. In another study, in marchigian sardinian (msP) alcohol-preferring rats, stress led to decreased methylation of Oprl1 in the nucleus accumbens and increased alcohol intake, suggesting an epigenetic mechanism in the influence of psychosocial stress on alcohol consumption [2]. In human alcoholics, the expression of Oprl1 mRNA was decreased in the central amygdala, potentially related to the impairment of cognitive control over alcohol-seeking behavior [5].

In conclusion, Oprl1 plays a crucial role in cognitive function, alcohol-related behaviors, and may be involved in the response to stress. Mouse models have been instrumental in revealing its role in cognitive impairment associated with adverse early-life environments and its contribution to alcohol-related behaviors. These findings highlight the potential of Oprl1 as a target for treating related cognitive and substance-abuse disorders.