Role of dopamine D1-family receptors in dorsolateral striatum in context-induced reinstatement of heroin seeking in rats

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 D₁-family receptors in lateral or medial accumbens shell, but not accumbens core. Objectives  In this study, we further characterized the role of striatal D₁-family receptors in context-induced reinstatement by assessing the effect of dorsolateral or dorsomedial injections of the D₁-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 D₁-family receptor antagonist SCH 23390 (0.3–1.0 μg 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 D₁-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 D₁-family dopamine receptors are critical for context-induced reinstatement of heroin seeking. Results also suggest that D₁-receptor-mediated dopamine transmission in the dorsolateral striatum and lateral accumbens shell independently support this reinstatement.