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Part VII. The Orbitofrontal Cortex and Addiction |
Orbitofrontal Cortex and Cognitive-Motivational Impairments in Psychostimulant AddictionEvidence from Experiments in the Non-human Primate
PETER OLAUSSONa,
J. DAVID JENTSCHb,
DILJA D. KRUEGERa,c,
NATALIE C. TRONSONa,d,
ANGUS C. NAIRNa AND
JANE R. TAYLORa
a Department of Psychiatry, Division of Molecular Psychiatry, Yale University, New Haven, Connecticut, USA b Department of Psychology, UCLA, Los Angeles, California, USA c The Picower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA d Department of Psychiatry & Behavioral Sciences, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA
Key Words: reversal learning • prefrontal cortex • proteomics
Address for correspondence: Department of Psychiatry, Division of Molecular Psychiatry, Yale University, CMHC, 34 Park St, New Haven, CT 06508. Voice: (203) 974 7752; fax: (203) 974 7897. peter.olausson{at}yale.edu
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.
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