Extinction of drug seeking: Neural circuits and approaches to augmentation

• Extinction training produces a robust reduction in drug seeking behavior.
• Extinction depends on a cortical–striatal pathway inhibits lateral hypothalamus.
• Extinction depends also on a cortical–hypothalamic–thalamic pathway.
• Extinction can be augmented via pharmacological or behavioral approaches.

Extinction training can reduce drug seeking behavior. This article reviews the neural circuits that contribute to extinction and approaches to enhancing the efficacy of extinction. Extinction of drug seeking depends on cortical-striatal-hypothalamic and cortical-hypothalamic-thalamic pathways. These pathways interface, in the hypothalamus and thalamus respectively, with the neural circuits controlling reinstatement of drug seeking. The actions of these pathways at lateral hypothalamic orexin neurons, and of perifornical/dorsomedial hypothalamic derived opioid peptides at kappa opioid receptors in the paraventricular thalamus, are important for inhibiting drug seeking. Despite effectively reducing or inhibiting drug seeking in the short term, extinguished drug seeking is prone to relapse. Three different strategies to augment extinction learning or retrieval are reviewed: pharmacological augmentation, retrieval – extinction training, and provision of extinction memory retrieval cues. These strategies have been used in animal models and with human drug users to enhance extinction or cue exposure treatments. They hold promise as novel strategies to promote abstinence from drug seeking.This article is part of a Special Issue entitled ‘NIDA 40th Anniversary Issue’.