Extinction of drug seeking.

Drug seeking behavior can be reduced or inhibited via extinction. The brain mechanisms for extinction of drug seeking are poorly understood but are of significant interest because of their potential to identify novel approaches that promote abstinence from drug taking. Here we review recent literature on the neural mechanisms for extinction in drug self-administration paradigms. First, we consider the brain regions important for extinction of drug seeking. Functional inactivation studies have identified infralimbic prefrontal cortex, nucleus accumbens shell, as well as medial dorsal hypothalamus in the expression of extinction of drug seeking. These structures have been implicated in extinction expression across several reinforcers including cocaine, heroin, and alcohol. Second, we consider molecular studies which show that extinction training is associated with plasticity in glutamatergic signaling in both nucleus accumbens shell and core, and that this training may reverse or ameliorate the neuroadaptations produced by chronic drug exposure and spontaneous withdrawal. Finally, we consider the neural circuitry for extinction of drug seeking. Functional disconnection and neuroanatomical tracing studies show that extinction expression depends, at least in part, on cortico-striatal-hypothalamic and cortico-hypothalalmic-thalamic pathways. Moreover, they indicate that the expression of extinction and reinstatement of drug seeking may depend on parallel pathways that converge within lateral hypothalamus and paraventricular thalamus.