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

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. 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. 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 A mu g 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. 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. 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.