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Adolescent cannabinoid exposure effects on natural reward seeking and learning in rats

Abstract

Rationale

Adolescence is characterized by endocannabinoid (ECB)-dependent refinement of neural circuits underlying emotion, learning, and motivation. As a result, adolescent cannabinoid receptor stimulation (ACRS) with phytocannabinoids or synthetic agonists like “Spice” cause robust and persistent changes in both behavior and circuit architecture in rodents, including in reward-related regions like medial prefrontal cortex and nucleus accumbens (NAc).

Objectives and methods

Here, we examine persistent effects of ACRS with the cannabinoid receptor 1/2 specific agonist WIN55-212,2 (WIN; 1.2 mg/kg/day, postnatal day (PD) 30–43), on natural reward-seeking behaviors and ECB system function in adult male Long Evans rats (PD 60+).

Results

WIN ACRS increased palatable food intake, and altered attribution of incentive salience to food cues in a sign-/goal-tracking paradigm. ACRS also blunted hunger-induced sucrose intake, and resulted in increased anandamide and oleoylethanolamide levels in NAc after acute food restriction not seen in controls. ACRS did not affect food neophobia or locomotor response to a novel environment, but did increase preference for exploring a novel environment.

Conclusions

These results demonstrate that ACRS causes long-term increases in natural reward-seeking behaviors and ECB system function that persist into adulthood, potentially increasing liability to excessive natural reward seeking later in life.

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Acknowledgements

We thank Erik Castillo, Jenny Cevallos, Stephanie Lenogue, Iohana Pagnoncelli, Gagandeep Lal, Christopher Cross, and Richard Dang for the assistance in treating adolescent rats, behavioral testing, behavioral scoring, and sample preparation.

Funding

These studies were funded by R00 DA035251, the UCI Office of Research, and the Irvine Center for Addiction Neuroscience.

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Correspondence to S. V. Mahler.

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Schoch, H., Huerta, M.Y., Ruiz, C.M. et al. Adolescent cannabinoid exposure effects on natural reward seeking and learning in rats. Psychopharmacology 235, 121–134 (2018). https://doi.org/10.1007/s00213-017-4749-8

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  • DOI: https://doi.org/10.1007/s00213-017-4749-8

Keywords

  • Autoshaping
  • Palatable food
  • Novelty
  • Endocannabinoid
  • Nucleus accumbens
  • Reward