Neural correlates of inflexible behavior in the orbitofrontal-amygdalar circuit after cocaine exposure.
Addiction is characterized by compulsive or inflexible behavior, observed both in the context of drug-seeking and in contexts unrelated to drugs. One possible contributor to these inflexible behaviors may be drug-induced dysfunction within circuits that support behavioral flexibility, including the basolateral amygdala (ABL) and the orbitofrontal cortex (OFC). Here we describe data demonstrating that chronic cocaine exposure causes long-lasting changes in encoding properties in the ABL and the OFC during learning and reversal in an odor-guided task. In particular, these data suggest that inflexible encoding in ABL neurons may be the proximal cause of cocaine-induced behavioral inflexibility, and that a loss of outcome-expectant encoding in OFC neurons could be a more distal contributor to this impairment. A similar mechanism of drug-induced orbitofrontal-amygdalar dysfunction may cause inflexible behavior when animals and addicts are exposed to drug-associated cues and contexts.
Stalnaker
Thomas A
TA
Department of Anatomy and Neurobiology, University of Maryland School of Medicine, Baltimore, MD 21201, USA. tstal002@umaryland.edu
Roesch
Matthew R
MR
Calu
Donna J
DJ
Burke
Kathryn A
KA
Singh
Teghpal
T
Schoenbaum
Geoffrey
G
D000679:Amygdala / Q000187:drug effects*; D000818:Animals; D001519:Behavior / Q000187:drug effects*; D001522:Behavior, Animal / Q000187:drug effects*; D003042:Cocaine / Q000494:pharmacology*; D019970:Cocaine-Related Disorders / Q000473:pathology / Q000503:physiopathology; D003657:Decision Making / Q000187:drug effects; D005625:Frontal Lobe / Q000187:drug effects*; D006801:Humans; D009474:Neurons / Q000187:drug effects*
D003042:Cocaine