Antagonism of the dopamine D1‐like receptor in mesocorticolimbic nuclei attenuates acute food deprivation‐induced reinstatement of heroin seeking in rats

Abstract

The neurotransmitter dopamine (DA) plays a critical role in both priming-and cue-induced reinstatement of extinguished drug-seeking behavior, but its role in stress-induced reinstatement is less clear. Our laboratory has recently demonstrated that systemic administration of the DA D1-like receptor antagonist, SCH 23390, attenuates acute food deprivation (FD) stress-induced reinstatement. The current study was designed to elucidate the brain regions critical to the effect of SCH 23390 on FD stress-induced reinstatement. Rats were trained to press a lever to self-administer heroin (0.1 mg/kg/inf) over a period of 10 days. Following training, heroin was removed leading to an extinction of lever pressing. Next, rats were tested for reinstatement twice, under extinction conditions: once following 21-48 h FD; and once under sated conditions. Prior to testing, SCH 23390 was administered into the nucleus accumbens (NAc) shell (0.0, 0.3, 0.6 μg/side), NAc core (0.0, 0.3, 0.6 μg/side), dorsomedial prefrontal cortex (dmPFC; 0.0, 0.2, 2.0 μg/side), ventromedial prefrontal cortex (vmPFC; 0.0, 2.0 μg/side) or basolateral amygdala (BLA; 0.0, 1.0, 2.0 μg/side). An attenuation of FD-induced reinstatement of heroin seeking was seen in rats injected with SCH 23390 into the NAc shell, dmPFC or BLA, but not into the NAc core or the vmPFC. These findings support the hypothesis that DA transmission through the DA D1-like receptors plays a critical role in stress-induced reinstatement of heroin seeking.

Augmentation of Heroin Seeking Following Chronic Food Restriction in the Rat: Differential Role for Dopamine Transmission in the Nucleus Accumbens Shell and Core

“…Previous studies suggest that DA D1-like receptors are important for context-and discriminative cue-induced reinstatement of heroin, cocaine, and natural rewards seeking . Moreover, we have recently reported that blockade of DA D1-, but not D2-like receptors, attenuated acute food deprivation-induced reinstatement of heroin seeking (Tobin et al, 2013). In addition, chronic food restriction increases synaptic plasticity in NAc cells expressing DA D1-like, but not D2-like, receptors (Carr et al, 2003(Carr et al, , 2010.…”

“…For rats in the microdialysis experiments, unilateral guide cannulae, counterbalanced between the right and left hemispheres, were implanted targeting the NAc shell (Experiment 1) or NAc core (Experiment 2) during the intravenous surgical procedure (Ito et al, 2000). For DA receptor antagonist administration, bilateral guide cannulae targeting the NAc shell (Experiment 3) or NAc core (Experiment 4) were implanted during the intravenous surgical procedure (Tobin et al, 2013). See also Supplementary Material.…”

The reinstatement model of drug relapse: recent neurobiological findings, emerging research topics, and translational research

“…Tobin et al (2013) recently performed a comprehensive study assessing the role of dopamine D1 receptors in different brain regions in acute 1-day food-deprivation-induced reinstatement of heroin seeking. They found that injections of the D1-family receptor antagonist SCH 23390 into accumbens shell, dorsal mPFC, and basolateral amygdala, but not accumbens core or ventral mPFC, decrease this reinstatement (Tobin et al 2013). An interpretation issue in this study is that SCH 23390 is also a 5-HT2C (formerly 5-HT1C) receptor agonist (Millan et al 2001).…”

Dopamine D1and D3Receptors Modulate Heroin-Induced Cognitive Impairment through Opponent Actions in Mice

“…Intracranial infusion of SCH-23390, an antagonist for dopamine D 1 -like receptors (including D 1 and D 5 receptors), into the prelimbic cortex potently and dose dependently attenuated heroin seeking in response to either cue presentations or a priming dose of heroin, suggesting that D 1 receptors regulate prefrontal pathways necessary for the reinstatement of heroin seeking (See, 2009). Attenuated reinstatement of heroin seeking was observed in rats injected with SCH-23390 into the NAc shell, suggesting that dopamine transmission in the NAc through the D 1 -like receptors plays a critical role in the drug reinforcement and motivational drive that promotes drug-seeking behavior (Tobin et al, 2013). Studies also revealed an attenuation of drug seeking following systemic administration of the D 3 receptor antagonist, SB-277011A (Xi et al, 2004).…”