title: Alterations in reward, fear and safety cue discrimination after inactivation of the rat prelimbic and infralimbic cortices.
abstract: Accurate discrimination of environmental cues predicting reward, fear, or safety is important for survival. The prelimbic and infralimbic cortices are implicated in regulating reward-seeking and fear behaviors; however, no studies have examined their roles in discriminating among reward, fear, and safety cues. Using a discriminative conditioning task that includes presentations of a reward cue (paired with a reward pellet), fear cue (paired with footshock), and a compound fear+safety cue (no footshock) within the same sessions allowed us to assess the flexibility and precision of fear and reward-seeking behaviors to these cues. We found that fear behavior was appropriately limited to the fear cue in untreated rats, but during infralimbic cortical inactivation, similar levels of fear were seen to the fear and compound fear+safety cues. Reward-seeking behavior was also appropriately limited to the reward cue in untreated rats. Inactivating the prelimbic cortex altered discriminative reward seeking as rats with prelimbic inactivation did not increase their reward seeking behavior during the reward cue to the same degree as saline controls. Our results imply dissociable roles of the two cortical regions: the prelimbic cortex in precise discriminative reward seeking and the infralimbic cortex in discriminating between fear and safety cues. These data suggest that alterations in the balance of activity between areas homologous to the prelimbic and infralimbic cortices may be involved in the processes that go awry in anxiety and addiction disorders.
authors.affiliation: Department of Physiology, University of Saskatchewan, Saskatoon, SK, Canada.
authors.forename: Susan
authors.initials: S
authors.lastname: Sangha
authors.affiliation: Department of Physiology, University of Saskatchewan, Saskatoon, SK, Canada.
authors.forename: Paul D
authors.initials: PD
authors.lastname: Robinson
authors.affiliation: Department of Physiology, University of Saskatchewan, Saskatoon, SK, Canada.
authors.forename: Quentin
authors.initials: Q
authors.lastname: Greba
authors.affiliation: Department of Physiology, University of Saskatchewan, Saskatoon, SK, Canada.
authors.forename: Don A
authors.initials: DA
authors.lastname: Davies
authors.affiliation: Department of Physiology, University of Saskatchewan, Saskatoon, SK, Canada.
authors.forename: John G
authors.initials: JG
authors.lastname: Howland
mesh_terms: D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D003213:Conditioning, Psychological / Q000502:physiology; D003463:Cues; D004192:Discrimination, Psychological / Q000502:physiology*; D004597:Electroshock; D005108:Extinction, Psychological / Q000502:physiology; D005239:Fear / Q000502:physiology*; D005502:Food; D058785:GABA-A Receptor Agonists / Q000494:pharmacology; D058786:GABA-B Receptor Agonists / Q000494:pharmacology; D008297:Male; D011939:Mental Recall / Q000502:physiology; D009118:Muscimol / Q000494:pharmacology; D017397:Prefrontal Cortex / Q000187:drug effects / Q000502:physiology*; D020318:Rats, Long-Evans; D012201:Reward
chemical_list: D058785:GABA-A Receptor Agonists; D058786:GABA-B Receptor Agonists; D009118:Muscimol; D001418:Baclofen
references.citation: J Neurosci. 2013 Feb 27;33(9):3744-51
references.pmid: 23447586
references.citation: Eur J Neurosci. 2013 Jan;37(2):259-68
references.pmid: 23106416
references.citation: Nature. 2010 Nov 11;468(7321):277-82
references.pmid: 21068837
references.citation: J Neurosci. 2001 Nov 1;21(21):8655-63
references.pmid: 11606653
references.citation: Neurobiol Learn Mem. 2011 Oct;96(3):417-31
references.pmid: 21855643
references.citation: Eur J Neurosci. 2006 Feb;23(3):758-64
references.pmid: 16487156
references.citation: J Neurosci. 2009 Jul 1;29(26):8474-82
references.pmid: 19571138
references.citation: Trends Neurosci. 2002 Jul;25(7):340-3
references.pmid: 12079756
references.citation: Behav Brain Res. 2011 Jun 20;220(1):238-43
references.pmid: 21316397
references.citation: J Neurosci. 2012 Oct 10;32(41):14118-24
references.pmid: 23055481
references.citation: J Comp Physiol Psychol. 1969 Mar;67(3):370-5
references.pmid: 5787388
references.citation: Neurosci Biobehav Rev. 2003 Oct;27(6):555-79
references.pmid: 14599436
references.citation: Eur J Neurosci. 2006 Sep;24(6):1751-8
references.pmid: 17004939
references.citation: Learn Mem. 2006 Nov-Dec;13(6):728-33
references.pmid: 17142302
references.citation: Psychiatry Res. 2009 May 15;167(1-2):151-60
references.pmid: 19345420
references.citation: Behav Neurosci. 1997 Aug;111(4):712-26
references.pmid: 9267649
references.citation: Cereb Cortex. 2014 Apr;24(4):1066-74
references.pmid: 23236210
references.citation: Neurosci Biobehav Rev. 2010 Nov;35(2):276-84
references.pmid: 19932711
references.citation: Nature. 2011 Mar 17;471(7338):358-62
references.pmid: 21389985
references.citation: Arch Gen Psychiatry. 2005 Jun;62(6):617-27
references.pmid: 15939839
references.citation: Cereb Cortex. 2003 Apr;13(4):400-8
references.pmid: 12631569
references.citation: Physiol Rev. 2010 Apr;90(2):419-63
references.pmid: 20393190
references.citation: Neuropsychopharmacology. 2011 Jan;36(2):529-38
references.pmid: 20962768
references.citation: Synapse. 2004 Jan;51(1):32-58
references.pmid: 14579424
references.citation: J Neurosci. 2008 Dec 10;28(50):13703-11
references.pmid: 19074043
references.citation: PLoS One. 2013;8(2):e57575
references.pmid: 23460877
references.citation: Biol Psychiatry. 2013 Feb 1;73(3):271-9
references.pmid: 22985696
references.citation: Biol Psychiatry. 2006 Aug 15;60(4):376-82
references.pmid: 16919525
references.citation: Learn Mem. 2009 Aug 25;16(9):520-9
references.pmid: 19706835
references.citation: Neuroscience. 2006 Sep 29;142(1):1-20
references.pmid: 16887277
references.citation: Eur J Neurosci. 2007 Jan;25(2):559-66
references.pmid: 17284198
references.citation: Learn Mem. 2011 Oct 17;18(11):688-92
references.pmid: 22005749
references.citation: BMC Biol. 2006 Apr 13;4:8
references.pmid: 16613600
references.citation: J Neurosci. 2007 Jan 24;27(4):840-4
references.pmid: 17251424
references.citation: Cereb Cortex. 2010 Aug;20(8):1816-28
references.pmid: 19892787
references.citation: Behav Brain Res. 2003 Nov 30;146(1-2):3-17
references.pmid: 14643455
references.citation: Trends Neurosci. 2008 Nov;31(11):552-8
references.pmid: 18786735