title: Control Over Stress Accelerates Extinction of Drug Seeking Via Prefrontal Cortical Activation.
abstract: Extinction is a form of inhibitory learning viewed as an essential process in suppressing conditioned responses to drug cues, yet there is little information concerning experiential variables that modulate its formation. Coping factors play an instrumental role in determining how adverse life events impact the transition from casual drug use to addiction. Here we provide evidence in rat that prior exposure to controllable stress accelerates the extinction of cocaine-seeking behavior relative to uncontrollable or no stress exposure. Subsequent experimentation using high-speed optogenetic tools determined if the infralimbic region (IL) of the ventral medial prefrontal cortex mediates the impact of controllable stress on cocaine-seeking behavior. Photoinhibition of pyramidal neurons in the IL during coping behavior did not interfere with subject's ability to control the stressor, but prevented the later control-induced facilitation of extinction. These results provide strong evidence that the degree of behavioral control over adverse events, rather than adverse eventsper se, potently modulates the extinction of cocaine-seeking behavior, and that controllable stress engages prefrontal circuitry that primes future extinction learning.
authors.affiliation: Institute for Behavioral Genetics, University of Colorado Boulder, Boulder, Colorado, 80309-0447, USA ; Department of Psychology and Neuroscience, University of Colorado Boulder, Boulder, Colorado, 80309-0447, USA.
authors.forename: Michael V
authors.initials: MV
authors.lastname: Baratta
authors.affiliation: Institute for Behavioral Genetics, University of Colorado Boulder, Boulder, Colorado, 80309-0447, USA.
authors.forename: Matthew B
authors.initials: MB
authors.lastname: Pomrenze
authors.affiliation: Institute for Behavioral Genetics, University of Colorado Boulder, Boulder, Colorado, 80309-0447, USA.
authors.forename: Shinya
authors.initials: S
authors.lastname: Nakamura
authors.affiliation: Institute for Behavioral Genetics, University of Colorado Boulder, Boulder, Colorado, 80309-0447, USA ; Department of Psychology and Neuroscience, University of Colorado Boulder, Boulder, Colorado, 80309-0447, USA.
authors.forename: Samuel D
authors.initials: SD
authors.lastname: Dolzani
authors.affiliation: Institute for Behavioral Genetics, University of Colorado Boulder, Boulder, Colorado, 80309-0447, USA ; Department of Psychology and Neuroscience, University of Colorado Boulder, Boulder, Colorado, 80309-0447, USA.
authors.forename: Donald C
authors.initials: DC
authors.lastname: Cooper
keywords: cocaine; coping; extinction; medial prefrontal cortex; optogenetics; resilience