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.

Automated summary

Adolescence is a critical period during which significant neurodevelopmental changes occur, and substance abuse during this stage can induce persistent changes in brain responsiveness. Binge-drinking behavior among adolescents is a growing concern, as alcohol is known to act as a gateway drug. This study aimed to assess the impact of adolescent ethanol exposure on tolerance and dependence to morphine, and found that it facilitates morphine tolerance but does not significantly alter dependence. Additionally, treatment with omega-3 fatty acids was found to prevent these ethanol-induced changes.