Sex differences in adolescent cannabis vapor self-administration mediate enduring effects on behavioral flexibility and prefrontal microglia activation in rats.

Autor: Freels TG; Department of Integrative Physiology and Neuroscience, Washington State University, Pullman, WA, USA., Westbrook SR; Department of Integrative Physiology and Neuroscience, Washington State University, Pullman, WA, USA., Wright HR; Department of Integrative Physiology and Neuroscience, Washington State University, Pullman, WA, USA., Kuyat JR; Department of Integrative Physiology and Neuroscience, Washington State University, Pullman, WA, USA., Zamberletti E; Department of Biotechnology and Life Sciences and Neuroscience Center, University of Insubria, Busto Arsizio, Varese, Italy., Malena AM; Department of Integrative Physiology and Neuroscience, Washington State University, Pullman, WA, USA., Melville MW; Department of Integrative Physiology and Neuroscience, Washington State University, Pullman, WA, USA., Brown AM; Department of Integrative Physiology and Neuroscience, Washington State University, Pullman, WA, USA., Glodosky NC; Department of Psychology, Washington State University, Pullman, WA, USA., Ginder DE; Department of Psychology, Washington State University, Pullman, WA, USA., Klappenbach CM; Department of Integrative Physiology and Neuroscience, Washington State University, Pullman, WA, USA., Delevich KM; Department of Integrative Physiology and Neuroscience, Washington State University, Pullman, WA, USA., Rubino T; Department of Biotechnology and Life Sciences and Neuroscience Center, University of Insubria, Busto Arsizio, Varese, Italy., McLaughlin RJ; Department of Integrative Physiology and Neuroscience, Washington State University, Pullman, WA, USA.; Department of Psychology, Washington State University, Pullman, WA, USA.
Jazyk: angličtina
Zdroj: BioRxiv : the preprint server for biology [bioRxiv] 2023 Jan 22. Date of Electronic Publication: 2023 Jan 22.
DOI: 10.1101/2023.01.21.524468
Abstrakt: Cannabis is the most used illicit drug in the United States. With many states passing legislation to permit its recreational use, there is concern that cannabis use among adolescents could increase dramatically in the coming years. Historically, it has been difficult to model real-world cannabis use to investigate the causal relationship between cannabis use in adolescence and behavioral and neurobiological effects in adulthood. To this end, we used a novel volitional vapor administration model to investigate long-term effects of cannabis use during adolescence on the medial prefrontal cortex (mPFC) and mPFC-dependent behaviors in male and female rats. Adolescent (35-55 day old) female rats had significantly higher rates of responding for vaporized Δ 9 -tetrahydrocannabinol (THC)-dominant cannabis extract (CAN THC ) compared to adolescent males. In adulthood (70-110 day old), female, but not male, CAN THC rats also took more trials to reach criterion and made more regressive errors in an automated attentional set-shifting task compared to vehicle rats. Similar set-shifting deficits were observed in males when they were exposed to a non-contingent CAN THC vapor dosing regimen that approximated CAN THC self-administration rates in females. No differences were observed in effort-based decision making in either sex. In the mPFC, female (but not male) CAN THC rats displayed more reactive microglia with no significant changes in myelin basic protein expression or dendritic spine density. Together, these data reveal important sex differences in rates of cannabis vapor self-administration in adolescence that confer enduring alterations to mPFC structure and function. Importantly, female-specific deficits in behavioral flexibility appear to be driven by elevated rates of CAN THC self-administration as opposed to a sex difference in the effects of CAN THC vapor per se .
Competing Interests: CONFLICT OF INTEREST STATEMENT: The authors have no competing personal or financial interests or any other conflicts of interest to disclose.
Databáze: MEDLINE
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