title: Endogenous Opioid Signaling in the Medial Prefrontal Cortex is Required for the Expression of Hunger-Induced Impulsive Action.
abstract: Opioid transmission and dysregulated prefrontal cortex (PFC) activity have both been implicated in the inhibitory-control deficits associated with addiction and binge-type eating disorders. What remains unknown, however, is whether endogenous opioid transmission within the PFC modulates inhibitory control. Here, we compared intra-PFC opioid manipulations with a monoamine manipulation (d-amphetamine), in two sucrose-reinforced tasks: progressive ratio (PR), which assays the motivational value of an incentive, and differential reinforcement of low response rates (DRLs), a test of inhibitory control. Intra-PFC methylnaloxonium (M-NX, a limited diffusion opioid antagonist) was given to rats in a 'low-drive' condition (2-h food deprivation), and also after a motivational shift to a 'high-drive' condition (18-h food deprivation). Intra-PFC DAMGO (D-[Ala2,N-MePhe4, Gly-ol]-enkephalin; a μ-opioid agonist) and d-amphetamine were also tested in both tasks, under the low-drive condition. Intra-PFC M-NX nearly eliminated impulsive action in DRL engendered by hunger, at a dose (1 μg) that significantly affected neither hunger-induced PR enhancement nor hyperactivity. At a higher dose (3 μg), M-NX eliminated impulsive action and returned PR breakpoint to low-drive levels. Conversely, intra-PFC DAMGO engendered 'high-drive-like' effects: enhancement of PR and impairment of DRL performance. Intra-PFC d-amphetamine failed to produce effects in either task. These results establish that endogenous PFC opioid transmission is both necessary and sufficient for the expression of impulsive action in a high-arousal, high-drive appetitive state, and that PFC-based opioid systems enact functionally unique effects on food impulsivity and motivation relative to PFC-based monoamine systems. Opioid antagonists may represent effective treatments for a range of psychiatric disorders with impulsivity features.
authors: Neuroscience Training Program, University of Wisconsin-Madison, School of Medicine and Public Health, Madison, WI, USA.
authors: Ryan A
authors: RA
authors: Selleck
authors: College of Agricultural and Life Sciences, University of Wisconsin-Madison, Madison, WI, USA.
authors: Curtis
authors: C
authors: Lake
authors: College of Arts and Sciences, University of Texas, San Antonio, San Antonio, TX, USA.
authors: Viridiana
authors: V
authors: Estrada
authors: College of Letters and Science, University of Wisconsin-Madison, Madison, WI, USA.
authors: Justin
authors: J
authors: Riederer
authors: Department of Psychology, University of Wisconsin-Whitewater, Whitewater, WI, USA.
authors: Matthew
authors: M
authors: Andrzejewski
authors: Department of Psychiatry, University of Wisconsin-Madison, School of Medicine and Public Health, Madison, WI, USA.
authors: Ken
authors: K
authors: Sadeghian
authors: 1] Neuroscience Training Program, University of Wisconsin-Madison, School of Medicine and Public Health, Madison, WI, USA [2] Department of Psychiatry, University of Wisconsin-Madison, School of Medicine and Public Health, Madison, WI, USA.
authors: Brian A
authors: BA
authors: Baldo
mesh_terms: D000661:Amphetamine / Q000494:pharmacology; D000701:Analgesics, Opioid / Q000378:metabolism* / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D003216:Conditioning, Operant / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)- / Q000494:pharmacology; D006815:Hunger; D007175:Impulsive Behavior / Q000502:physiology*; D008297:Male; D009270:Naloxone / Q000031:analogs & derivatives / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D017397:Prefrontal Cortex / Q000378:metabolism*; D000644:Quaternary Ammonium Compounds / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D000701:Analgesics, Opioid; D009292:Narcotic Antagonists; D000644:Quaternary Ammonium Compounds; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D009270:Naloxone; C041269:N-methylnaloxone; D000661:Amphetamine