Orbitofrontal cortex and cognitive-motivational impairments in psychostimulant addiction: evidence from experiments in the non-human primate.
Addiction is characterized by compulsive drug use despite adverse consequences. The precise psychobiological changes that underlie the progression from casual use to loss of control over drug-seeking and drug-taking behavior are not well understood. Here we report that short-term cocaine exposure in monkeys is sufficient to produce both selective deficits in cognitive functions dependent on the orbitofrontal cortex (OFC) concurrent with enhancements in motivational processes involving limbic-striatal regions. Additional findings from behavioral studies and analyses of the synaptic proteome provide new behavioral and biochemical evidence that cocaine-induced neuroadaptations in cortical and subcortical brain regions result in dysfunctional decision-making abilities and loss of impulse control that in combination with enhancements of incentive motivation may contribute to the development of compulsive behavior in addiction.
Olausson
Peter
P
Department of Psychiatry, Division of Molecular Psychiatry, Yale University, New Haven, CT 06508, USA. peter.olausson@yale.edu
Jentsch
J David
JD
Krueger
Dilja D
DD
Tronson
Natalie C
NC
Nairn
Angus C
AC
Taylor
Jane R
JR
D000222:Adaptation, Physiological; D000818:Animals; D016739:Behavior, Addictive / Q000139:chemically induced* / Q000523:psychology*; D003042:Cocaine / Q000494:pharmacology; D003072:Cognition Disorders / Q000139:chemically induced* / Q000523:psychology*; D005625:Frontal Lobe / Q000502:physiology*; D011323:Primates / Q000502:physiology*; D040901:Proteomics
D003042:Cocaine