Abstract
Adolescent binge drinking is associated with an increased risk of substance use disorder, but how ethanol affects the central levels of endogenous opioid peptides is still not thoroughly investigated. The aim of this study was to examine the effect of repeated episodic ethanol exposure during adolescence on the tissue levels of three different endogenous opioid peptides in rats. Outbred Wistar rats received orogastric (i.e., gavage) ethanol for three consecutive days per week between 4 and 9 weeks of age. At 2 h and 3 weeks, respectively, after the last exposure, beta-endorphin, dynorphin B and Met-enkephalin-Arg6Phe7 (MEAP) were analyzed with radioimmunoassay. Beta-endorphin levels were low in the nucleus accumbens during ethanol intoxication. Remaining effects of adolescent ethanol exposure were found especially for MEAP, with low levels in the amygdala, and high in the substantia nigra and ventral tegmental area three weeks after the last exposure. In the hypothalamus and pituitary, the effects of ethanol on beta-endorphin were dependent on time from the last exposure. An interaction effect was also found in the accumbal levels of MEAP and nigral dynorphin B. These results demonstrate that repeated episodic exposure to ethanol during adolescence affected opioid peptide levels in regions involved in reward and reinforcement as well as stress response. These alterations in opioid networks after adolescent ethanol exposure could explain, in part, the increased risk for high ethanol consumption later in life.
Highlights
During adolescence, social interactions with peers become highly important and increased frequencies in behaviors like risk-taking, impulsivity and novelty-seeking can be observed in experimental models [1]
Intoxication after repeated ethanol exposure during adolescence altered the levels of MEAP and beta-endorphin in the accumbens and dynorphin B and MEAP in the pituitary
Noteworthy is the observation of long-term consequences of the adolescent ethanol exposure, MEAP in the amygdala and beta-endorphin in the hypothalamus and pituitary as these regions are involved in the response to anxiety and stress
Summary
Social interactions with peers become highly important and increased frequencies in behaviors like risk-taking, impulsivity and novelty-seeking can be observed in experimental models [1]. Exposure to ethanol may pose risks as indicated by findings showing that early onset of drug consumption can increase later susceptibility for drug abuse and addiction [4,5,6,7]. This vulnerability could be a result of three factors [8]. As the adolescent brain continually matures, early use might shape the brain toward a vulnerability state, which leads to later susceptibility for drug use. To investigate the third factor, an adolescent rat model was used to study the endogenous opioid system after episodic binges of ethanol
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