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

Abstract

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. 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. 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. 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 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.