D1-like and D2 dopamine receptor antagonists administered into the shell subregion of the rat nucleus accumbens decrease cocaine, but not food, reinforcement

Neuroscience. 2005;135(3):959-68. doi: 10.1016/j.neuroscience.2005.06.048. Epub 2005 Aug 19.


Cocaine self-administration experiments were designed to assess the respective roles of D1-like and D2-like dopamine receptors in the ventral forebrain in cocaine reinforcement. D1-like or D2-like dopamine receptor antagonists were microinjected into the nucleus accumbens core, nucleus accumbens shell, neostriatum or lateral septum prior to sessions in which cocaine was self-administered under a progressive ratio schedule by rats. The results indicated that administration of a D1/5 (SCH-23390) or a D2/D3/D4 (eticlopride), but not a D3 (U99194A) or D4 (L-750,667), dopamine receptor antagonist into the core and shell of the nucleus accumbens decreased the reinforcing efficacy of cocaine. However, in control experiments intra-accumbal core administration of SCH-23390 or eticlopride decreased food self-administration, whereas administration of these drugs into the accumbens shell had no effect on food reinforcement. Neither SCH-23390 nor eticlopride influenced cocaine reinforcement when administered into the neostriatum or lateral septum. Collectively, these results indicate that D1-like and D2 dopamine receptors in the nucleus accumbens shell selectively modulate the reinforcing efficacy of cocaine, whereas D1-like and D2 dopamine receptors in the accumbens core have a more general influence on reinforced behaviors.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Benzazepines / administration & dosage
  • Benzazepines / pharmacology
  • Cocaine / administration & dosage
  • Cocaine / antagonists & inhibitors*
  • Cocaine / pharmacology*
  • Conditioning, Operant / drug effects
  • Dopamine Antagonists / administration & dosage
  • Dopamine Antagonists / pharmacology*
  • Dopamine D2 Receptor Antagonists*
  • Dose-Response Relationship, Drug
  • Food*
  • Injections, Intravenous
  • Male
  • Microinjections
  • Nucleus Accumbens / physiology*
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Dopamine D1 / antagonists & inhibitors*
  • Receptors, Dopamine D3 / antagonists & inhibitors
  • Receptors, Dopamine D4 / antagonists & inhibitors
  • Receptors, Dopamine D5 / antagonists & inhibitors
  • Reinforcement, Psychology*
  • Salicylamides / administration & dosage
  • Salicylamides / pharmacology
  • Self Administration


  • Benzazepines
  • Dopamine Antagonists
  • Dopamine D2 Receptor Antagonists
  • Receptors, Dopamine D1
  • Receptors, Dopamine D3
  • Salicylamides
  • Receptors, Dopamine D4
  • Receptors, Dopamine D5
  • Cocaine
  • eticlopride