Monitoring extracellular dopamine in the rat nucleus accumbens shell and core during acquisition and maintenance of intravenous WIN 55,212-2 self-administration

Psychopharmacology (Berl). 2006 Sep;188(1):63-74. doi: 10.1007/s00213-006-0475-3. Epub 2006 Jul 19.


Rationale: WIN 55,212-2, a potent cannabinoid receptor 1 agonist, is self-administered by animals to evaluate abuse liability of cannabinoids, but to date no information is yet available about its effects on dopaminergic transmission during active response-contingent administration.

Objectives: This study monitored the changes of extracellular dopamine (DA) in the nucleus accumbens (NAc) shell and core during active intravenous WIN 55,212-2 self-administration (SA).

Methods: Rats, implanted with a jugular catheter and bilateral intracerebral chronic cannulae, were trained for 3 weeks to self-administer WIN 55,212-2 (12.5 microg/kg) in single daily 1-h sessions under a fixed ratio 1 (FR 1) schedule, than switched to FR 2 for a further week. During SA sessions, microdialysis assays were performed every 3rd day, and then daily starting from the 13th session. Dialysate DA from the NAc shell and core was monitored before, during, and for 30 min after SA.

Results: Dialysate DA increased during WIN 55,212-2 SA starting from the 1st week in the NAc shell and on the 2nd week in the core. The increase of dialysate DA in the NAc shell was larger than that in the core on all weeks. Dialysate DA did not change during extinction sessions in spite of active nose poking.

Conclusions: Response-contingent WIN 55,212-2 SA preferentially increases the NAc shell DA output as compared to that of the core independently from the duration of the WIN 55,212-2 exposure. Increase in NAc DA is strictly related to WIN 55,212-2 actions because it is not observed during extinction despite active responding.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Benzoxazines
  • Cannabinoids / administration & dosage
  • Cannabinoids / pharmacology*
  • Conditioning, Operant
  • Dopamine / metabolism*
  • Extinction, Psychological
  • Extracellular Fluid / drug effects*
  • Extracellular Fluid / metabolism
  • Infusions, Intravenous
  • Male
  • Microdialysis
  • Morpholines / administration & dosage
  • Morpholines / pharmacology*
  • Naphthalenes / administration & dosage
  • Naphthalenes / pharmacology*
  • Nucleus Accumbens / cytology
  • Nucleus Accumbens / drug effects*
  • Nucleus Accumbens / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Receptor, Cannabinoid, CB1 / agonists
  • Receptor, Cannabinoid, CB1 / metabolism
  • Regression Analysis
  • Reinforcement Schedule
  • Self Administration
  • Time Factors


  • Benzoxazines
  • Cannabinoids
  • Morpholines
  • Naphthalenes
  • Receptor, Cannabinoid, CB1
  • (3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone
  • Dopamine