A history of ethanol intake accelerates the development of morphine analgesic tolerance: A protective potential for omega-3 fatty acids.

Adolescence is a critical life period during which significant neurodevelopmental changes occur within the central nervous system. Consistently, substance abuse in this stage has been found to induce persistent changes in brain responsiveness to future drug challenges. Nowadays, heavy episodic alcohol consumption during adolescence, also known as binge-drinking behavior, is a growing concern in modern societies. On the other hand, alcohol is well known to act as a gateway drug, that is, it promotes the individual's craving for consumption of other drugs of abuse. With this in mind, we aimed to assess whether adolescent ethanol exposure could alter the development of tolerance and dependence to morphine, as an available common opioid drug. Tail flick test was used to measure thermal nociceptive changes in adult male Wistar rats undergone ethanol/vehicle exposure during adolescence. Furthermore, morphine withdrawal syndrome was induced by naloxone injection, and behavioral signs were recorded for 20 min. It was found that adolescent ethanol intake facilitates morphine analgesic tolerance and decreases baseline latency; however, the severity of dependence is not significantly altered. Moreover, we found that 15 days of treatment with omega-3 fatty acids (O3) prevents the mentioned ethanol-induced changes suggesting a therapeutic potential for this compound. O3 supplementation, as an inexpensive and noninvasive method, may assist the clinicians to reverse the adverse effect of alcohol binge drinking on adolescents' brains and to reduce the vulnerability to drug exposure in adulthood. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Intermittent REM sleep deprivation attenuates the development of morphine tolerance and dependence in male rats.

Opioid agonists are used in clinic for pain management, however this application is challenged by development of tolerance and dependence following prolonged exposure. Various approaches have been suggested to address this concern, however, there is still no consensus among the researchers. Neural processing of sleep and nociception are co-regulated through shared brain regions having bidirectional interplays. Thus, we aimed to investigate whether application of REM sleep deprivation (REM-SD) could affect morphine analgesic tolerance and dependence. To this end, adult male rats underwent sleep deprivation during light and dark phases (LSD and DSD, respectively) using the inverted flower pot method and then tolerance and dependence was induced by repeated injection of morphine for 7 days (10 mg/kg, daily, i.p.). Results indicated that REM-SD delays the development of tolerance to morphine during both phases; however this effect was more potent following LSD. Moreover, LSD decreased the baseline thermal threshold and total withdrawal score. One possible hypothesis for our observations is REM-SD-induced attenuation of orexin system which is still controversial among the researchers. Other stronger possibilities might be down-regulation of opioid receptors in response to sleep loss experience. Finally, it seems that modification of sleep periods may assist to decrease the severity of opioid tolerance and dependence.

Coregulation of sleep-pain physiological interplay by orexin system: An unprecedented review.

Accumulating evidence support the critical role of endogenous orexin system in modulation of various physiological functions. Among these, regulation of pain and wakefulness have extensively been investigated, however, by independent series of studies each focusing a distinct side. It is now well established that orexins induce potent analgesic effect via affecting their receptors within several specific brain structures. These mainly include locus coeruleus (LC), lateral paragigantocellularis (LPGi), ventral tegmental area (VTA), dorsal raphe nucleus (DRN), periaquiductal gray (PAG) and tuberomammillary nuclei (TMN). On the other hand, increased activity of orexinergic neurons enhances general wakefulness. Interestingly, a review of literature reveals that brain regions underlying orexin-mediated analgesia are most probably the site of action for orexin wake-promoting effects as well. The present study first pieces together the existing evidence supporting the rationale for the possibility of sleep-pain coregulation by orexin system and then suggests several shared mechanisms through which orexin can control the two mentioned processes. Furthermore, this study explains how imbalanced orexinergic transmission can cause progressive dysregulation of sleep-pain processing.