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bioRxiv · 10.1101/2022.09.20.508728

Adolescent ethanol exposure promotes mechanical allodynia and alters dopamine transmission in the nucleus accumbens shell.

Kelley, A. M.·Del Valle, E. J.·Zaman, S.·Karkhanis, A. N.
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Abstract

Excessive alcohol consumption in adolescence can disrupt neural development and may augment pain perception. Recent studies have shown that the nucleus accumbens (NAc) shell is involved in mediating pain sensitivity after peripheral inflammation in rodent models of chronic pain and alcohol use disorder (AUD). Interestingly, there have been very few studies examining the impact of chronic ethanol exposure during adolescence on pain sensitivity in adulthood. Therefore, in this project we investigated the impact of adolescent chronic intermittent ethanol (aCIE) exposure on mechanical allodynia and thermal hyperalgesia. Furthermore, given the involvement of the NAc shell in pain processing and chronic ethanol mediated changes, we measured changes in accumbal dopamine kinetics during protracted withdrawal. We found that both male and female aCIE rats show mechanical allodynia during withdrawal; however, only male rats exhibit thermal hyperalgesia during protracted withdrawal. Furthermore, male and female aCIE rats show greater evoked tonic dopamine release, maximal rate of dopamine reuptake, and dopamine affinity to the dopamine transporter in the NAc shell compared to controls. With phasic stimulation, aCIE rats also showed greater dopamine release compared to air exposed rats. These data suggest that aCIE exposure exacerbates pain sensitivity during withdrawal. Furthermore, based on prior literature, it is possible that the increased pain sensitivity may be driven, at least in part, by augmented dopamine kinetics in the NAc shell observed in the current study.

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Kelley, A. M., Del Valle, E. J., Zaman, S., Karkhanis, A. N.. 2022-09-22. Adolescent ethanol exposure promotes mechanical allodynia and alters dopamine transmission in the nucleus accumbens shell.. https://doi.org/10.1101/2022.09.20.508728

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