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

Psychopharmacology (Berl). 2018 Jan;235(1):121-134. doi: 10.1007/s00213-017-4749-8. Epub 2017 Oct 11.

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.

Keywords: Autoshaping; Endocannabinoid; Novelty; Nucleus accumbens; Palatable food; Reward.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arachidonic Acids / metabolism
  • Behavior, Animal / drug effects
  • Benzoxazines / pharmacology*
  • Cannabinoids / pharmacology*
  • Eating / drug effects
  • Endocannabinoids / metabolism*
  • Male
  • Morpholines / pharmacology*
  • Motivation / drug effects*
  • Naphthalenes / pharmacology*
  • Nucleus Accumbens / drug effects*
  • Nucleus Accumbens / metabolism
  • Oleic Acids / metabolism
  • Polyunsaturated Alkamides / metabolism
  • Rats
  • Rats, Long-Evans
  • Rats, Sprague-Dawley
  • Reward*

Substances

  • Arachidonic Acids
  • Benzoxazines
  • Cannabinoids
  • Endocannabinoids
  • Morpholines
  • Naphthalenes
  • Oleic Acids
  • Polyunsaturated Alkamides
  • oleoylethanolamide
  • (3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone
  • anandamide