Sex Differences in Response-Contingent Cannabis Vapor Administration During Adolescence 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, Washington, USA., Westbrook SR; Department of Integrative Physiology and Neuroscience, Washington State University, Pullman, Washington, USA., Zamberletti E; Department of Biotechnology and Life Sciences and Neuroscience Center, University of Insubria, Busto Arsizio, Varese, Italy., Kuyat JR; Department of Integrative Physiology and Neuroscience, Washington State University, Pullman, Washington, USA., Wright HR; Department of Integrative Physiology and Neuroscience, Washington State University, Pullman, Washington, USA., Malena AN; Department of Integrative Physiology and Neuroscience, Washington State University, Pullman, Washington, USA., Melville MW; Department of Integrative Physiology and Neuroscience, Washington State University, Pullman, Washington, USA., Brown AM; Department of Integrative Physiology and Neuroscience, Washington State University, Pullman, Washington, USA., Glodosky NC; Department of Psychology, Washington State University, Pullman, Washington, USA., Ginder DE; Department of Psychology, Washington State University, Pullman, Washington, USA., Klappenbach CM; Department of Integrative Physiology and Neuroscience, Washington State University, Pullman, Washington, USA., Delevich KM; Department of Integrative Physiology and Neuroscience, Washington State University, Pullman, Washington, 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, Washington, USA.; Department of Psychology, Washington State University, Pullman, Washington, USA.
Jazyk: angličtina
Zdroj: Cannabis and cannabinoid research [Cannabis Cannabinoid Res] 2024 Aug; Vol. 9 (4), pp. e1184-e1196. Date of Electronic Publication: 2024 Jan 08.
DOI: 10.1089/can.2023.0014
Abstrakt: Introduction: 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. Materials and Methods: We used a response-contingent 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. Results: Adolescent (35- to 55-day-old) female rats had significantly higher rates of responding for vaporized Δ 9 -tetrahydrocannabinol (THC)-dominant cannabis extract (CAN THC ) compared with adolescent males. In adulthood (70-110 days 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 with vehicle rats, thereby indicating sex differences in behavioral flexibility impairments. Notably, sex-treatment interactions were not observed when rats of each sex were exposed to a noncontingent CAN THC vapor dosing regimen that approximated CAN THC vapor deliveries earned by 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 changes in myelin basic protein expression or dendritic spine density. Conclusion: Altogether, these data reveal important sex differences in rates of responding for CAN THC vapor in adolescence that may confer enduring alterations to mPFC structure and function and suggest that there may be subtle differences in the effects of response-contingent versus noncontingent cannabis exposure that should be systematically examined in future studies.
Databáze: MEDLINE
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