Orbitofrontal cortex and cognitive-motivational impairments in psychostimulant addiction

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.