Role of dopamine D(1)-family receptors in dorsolateral striatum in context-induced reinstatement of heroin seeking in rats

Psychopharmacology (Berl). 2009 Sep;206(1):51-60. doi: 10.1007/s00213-009-1580-x. Epub 2009 Jun 9.


Rationale: In humans, exposure to environmental contexts previously associated with heroin intake can provoke relapse to drug use. In rats, exposure to heroin-associated contexts after extinction of drug-reinforced responding in different contexts reinstates heroin seeking. This effect is attenuated by blockade of D(1)-family receptors in lateral or medial accumbens shell, but not accumbens core.

Objectives: In this study, we further characterized the role of striatal D(1)-family receptors in context-induced reinstatement by assessing the effect of dorsolateral or dorsomedial injections of the D(1)-family receptor antagonist SCH 23390 on this reinstatement.

Materials and methods: Rats were trained to self-administer heroin (0.05-0.10 mg/kg per infusion) for 12 days; drug infusions were paired with a discrete tone-light cue. Subsequently, heroin-reinforced lever pressing was extinguished in the presence of the discrete cue in a nondrug context. During reinstatement tests under extinction conditions, the D(1)-family receptor antagonist SCH 23390 (0.3-1.0 microg per side) was injected into the dorsolateral or dorsomedial striatum prior to exposure to heroin self-administration context or the nondrug (extinction) context. We then used a disconnection procedure to examine whether D(1)-family receptors in the dorsolateral striatum and lateral accumbens shell jointly or independently support context-induced reinstatement.

Results: Dorsolateral but not dorsomedial SCH 23390 injections attenuated context-induced reinstatement of heroin seeking. SCH 23390 injections into the dorsolateral striatum of one hemisphere and lateral accumbens shell of the other hemisphere were ineffective.

Conclusions: Results indicate that dorsolateral striatum D(1)-family dopamine receptors are critical for context-induced reinstatement of heroin seeking. Results also suggest that D(1)-receptor-mediated dopamine transmission in the dorsolateral striatum and lateral accumbens shell independently support this reinstatement.

Publication types

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

MeSH terms

  • Animals
  • Behavior, Addictive / physiopathology*
  • Behavior, Animal / drug effects
  • Behavior, Animal / physiology
  • Benzazepines / pharmacology*
  • Conditioning, Psychological / drug effects
  • Conditioning, Psychological / physiology
  • Corpus Striatum / drug effects
  • Corpus Striatum / metabolism*
  • Disease Models, Animal
  • Extinction, Psychological / drug effects
  • Extinction, Psychological / physiology
  • Heroin / administration & dosage*
  • Heroin / pharmacology
  • Heroin Dependence / metabolism
  • Heroin Dependence / physiopathology
  • Male
  • Nucleus Accumbens / drug effects
  • Nucleus Accumbens / metabolism
  • Rats
  • Rats, Long-Evans
  • Receptors, Dopamine D1 / antagonists & inhibitors
  • Receptors, Dopamine D1 / physiology*
  • Reinforcement Schedule
  • Reward
  • Secondary Prevention
  • Self Administration


  • Benzazepines
  • Receptors, Dopamine D1
  • SCH 23390
  • Heroin