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Adolescent THC exposure: effects on pain-related, exploratory, and consummatory behaviors in adult male vs. female rats

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Abstract

Rationale

Adolescent cannabinoid exposure has been shown to alter cognitive, reward-related, and motor behaviors as well as mesocorticolimbic dopamine (DA) function in adult animals. Pain is also influenced by mesocorticolimbic DA function, but it is not known whether pain or cannabinoid analgesia in adults is altered by early exposure to cannabinoids.

Objective

To determine whether adolescent Δ9-tetrahydrocannabinol (THC) exposure alters pain-related behaviors before and after induction of persistent inflammatory pain, and whether it influences antinociceptive of THC, in adult rats, and to compare the impact of adolescent THC exposure on pain to its effects on known DA-dependent behaviors such as exploration and consumption of a sweet solution.

Methods

Vehicle or THC (2.5 to 10 mg/kg s.c.) was administered daily to male and female rats on post-natal day (PND) 30–43. In adulthood (PND 80–88), sensitivity to mechanical and thermal stimuli before and after intraplantar injection of complete Freund’s adjuvant (CFA) was determined. Antinociceptive, exploratory, and consummatory effects of 2.0 mg/kg THC were then examined.

Results

Adolescent THC exposure did not significantly alter adult sensitivity to non-noxious or noxious stimuli either before or after CFA injection, nor did it alter the antinociceptive effect of THC. In contrast, adolescent THC exposure altered adult exploratory and consummatory behaviors in a sex-dependent manner: when tested as adults, adolescent THC-treated males showed less hedonic drinking than adolescent vehicle-treated males, and females but not males that had been THC-exposed as adolescents showed reduced sensitivity to THC-induced suppression of activity and THC-induced hedonic drinking as adults.

Conclusions

Adolescent THC exposure that altered both exploratory and consummatory behaviors in adults did not alter pain-related behaviors either before or after induction of inflammatory pain, suggesting that cannabinoid exposure during adolescence is not likely to substantially alter pain or cannabinoid analgesia in adulthood.

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Acknowledgements

The authors thank I. McCaughran for technical assistance.

Funding

This research was supported by a Herbert L. Eastlick Professorship from the College of Arts and Sciences at Washington State University (to R.C.).

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Correspondence to Rebecca M. Craft.

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The authors declare no competing interests.

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This article belongs to a Special Issue on Cannabis and Cannabinoids

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Gogulski, H.Y., Craft, R.M. Adolescent THC exposure: effects on pain-related, exploratory, and consummatory behaviors in adult male vs. female rats. Psychopharmacology 239, 1563–1578 (2022). https://doi.org/10.1007/s00213-022-06094-9

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  • DOI: https://doi.org/10.1007/s00213-022-06094-9

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