Effects of Cocaine Self-Administration and Its Extinction on the Rat Brain Cannabinoid CB1 and CB2 Receptors

Neurotox Res. 2018 Oct;34(3):547-558. doi: 10.1007/s12640-018-9910-6. Epub 2018 May 12.


The aim of this study was to evaluate changes in the expression of cannabinoid type 1 (CB1) and 2 (CB2) receptor proteins in several brain regions in rats undergoing cocaine self-administration and extinction training. We used a triad-yoked procedure to distinguish between the motivational and pharmacological effects of cocaine. Using immunohistochemistry, we observed a significant decrease in CB1 receptor expression in the prefrontal cortex, dorsal striatum, and the basolateral and basomedial amygdala following cocaine (0.5 mg/kg/infusion) self-administration. Increased CB1 receptor expression in the ventral tegmental area in rats with previous cocaine exposure was also found. Following cocaine abstinence after 10 days of extinction training, we detected increases in the expression of CB1 receptors in the substantia nigra in both cocaine groups and in the subregions of the amygdala for only the yoked cocaine controls, while any method of cocaine exposure resulted in a decrease in CB2 receptor expression in the prefrontal cortex (p < 0.01), nucleus accumbens (p < 0.01), and medial globus pallidus (p < 0.01). Our findings further support the idea that the eCB system and CB1 receptors are involved in cocaine-reinforced behaviors. Moreover, we detected a cocaine-evoked adaptation in CB2 receptors in the amygdala, prefrontal cortex, and globus pallidus.

Keywords: Cannabinoid receptors; Cocaine addiction; Cocaine self-administration; Immunohistochemistry.

MeSH terms

  • Animals
  • Brain / drug effects*
  • Brain / metabolism
  • Cocaine / administration & dosage*
  • Cocaine / pharmacology*
  • Conditioning, Operant / drug effects
  • Dopamine Uptake Inhibitors / administration & dosage
  • Dopamine Uptake Inhibitors / pharmacology
  • Extinction, Psychological / drug effects*
  • Gene Expression Regulation / drug effects
  • Male
  • Rats
  • Rats, Wistar
  • Receptor, Cannabinoid, CB1 / metabolism*
  • Receptor, Cannabinoid, CB2 / metabolism*
  • Self Administration
  • Statistics, Nonparametric


  • Dopamine Uptake Inhibitors
  • Receptor, Cannabinoid, CB1
  • Receptor, Cannabinoid, CB2
  • Cocaine