TY - JOUR
T1 - Extinction of drug seeking
AU - Millan, E. Zayra
AU - Marchant, Nathan J.
AU - McNally, Gavan P.
PY - 2011/3/1
Y1 - 2011/3/1
N2 - 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.
AB - 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.
KW - Cocaine
KW - Drug
KW - Extinction
KW - Glutamate
KW - Nucleus accumbens
KW - Prefrontal cortex
UR - http://www.scopus.com/inward/record.url?scp=78650417799&partnerID=8YFLogxK
U2 - https://doi.org/10.1016/j.bbr.2010.10.037
DO - https://doi.org/10.1016/j.bbr.2010.10.037
M3 - Review article
C2 - 21073904
SN - 0166-4328
VL - 217
SP - 454
EP - 462
JO - Behavioural Brain Research
JF - Behavioural Brain Research
IS - 2
ER -