title: Developmental disruption of gamma-aminobutyric acid function in the medial prefrontal cortex by noncontingent cocaine exposure during early adolescence.
abstract: BACKGROUND
  Drug experimentation during adolescence is associated with increased risk of drug addiction relative to any other age group. To further understand the neurobiology underlying such liability, we investigate how early adolescent cocaine experience impacts medial prefrontal cortex (mPFC) network function in adulthood.
  
  
  METHODS
  A noncontingent administration paradigm was used to assess the impact of early adolescent cocaine treatment (rats; postnatal days [PD] 35-40) on the overall inhibitory regulation of mPFC activity in adulthood (PD 65-75) by means of histochemical and in vivo electrophysiological measures combined with pharmacologic manipulations.
  
  
  RESULTS
  Cocaine exposure during early adolescence yields a distinctive hypermetabolic prefrontal cortex state that was not observed in adult-treated rats (PD 75-80). Local field potential recordings revealed that early adolescent cocaine exposure is associated with an attenuation of mPFC gamma-aminobutyric acid (GABA)ergic inhibition evoked by ventral hippocampal stimulation at beta and gamma frequencies that endures throughout adulthood. Such cocaine-induced mPFC disinhibition was not observed in adult-exposed animals. Furthermore, the normal developmental upregulation of parvalbumin immunoreactivity observed in the mPFC from PD 35 to PD 65 is lacking following early adolescent cocaine treatment.
  
  
  CONCLUSIONS
  Our data indicate that repeated cocaine exposure during early adolescence can elicit a state of mPFC disinhibition resulting from a functional impairment of the local prefrontal GABAergic network that endures through adulthood. A lack of acquisition of prefrontal GABAergic function during adolescence could trigger long-term deficits in the mPFC that may increase the susceptibility for the onset of substance abuse and related psychiatric disorders.
authors.affiliation: Department of Cellular and Molecular Pharmacology, The Chicago Medical School at Rosalind Franklin University of Medicine and Science, North Chicago, Illinois.
authors.forename: Daryn K
authors.initials: DK
authors.lastname: Cass
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Thomases
authors.forename: Adriana
authors.initials: A
authors.lastname: Caballero
authors.forename: Kuei Y
authors.initials: KY
authors.lastname: Tseng
mesh_terms: D000367:Age Factors; D000818:Animals; D001569:Benzodiazepines / Q000494:pharmacology; D003042:Cocaine / Q000633:toxicity*; D018756:GABA Antagonists / Q000494:pharmacology; D018757:GABA Modulators / Q000494:pharmacology; D059330:GABAergic Neurons / Q000378:metabolism; D006624:Hippocampus / Q000503:physiopathology*; D008297:Male; D009433:Neural Inhibition; D009434:Neural Pathways; D010852:Picrotoxin / Q000494:pharmacology; D017397:Prefrontal Cortex / Q000378:metabolism / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000187:drug effects / Q000502:physiology*; D013876:Thiophenes / Q000494:pharmacology
chemical_list: D001569:Benzodiazepines; D003042:Cocaine; D018756:GABA Antagonists; D018757:GABA Modulators; D010852:Picrotoxin; D011963:Receptors, GABA-A; D013876:Thiophenes; C469870:indiplon
keywords: Adolescence; GABA; cocaine; electrophysiology; parvalbumin; prefrontal cortex
references.citation: Neuroimage. 1998 May;7(4 Pt 1):296-303
references.pmid: 9626670
references.citation: Neuropsychopharmacology. 2010 Oct;35(11):2292-304
references.pmid: 20664581
references.citation: Neuropharmacology. 2004;47 Suppl 1:47-60
references.pmid: 15464125
references.citation: J Neurosci. 2013 Jan 2;33(1):26-34
references.pmid: 23283319
references.citation: J Neurosci. 2001 Nov 1;21(21):8655-63
references.pmid: 11606653
references.citation: J Neuropsychiatry Clin Neurosci. 2004 Fall;16(4):456-64
references.pmid: 15616172
references.citation: J Neurosci. 2000 Nov 15;20(22):RC106
references.pmid: 11069975
references.citation: Schizophr Bull. 2011 May;37(3):484-92
references.pmid: 21505115
references.citation: Am J Psychiatry. 2002 Oct;159(10):1642-52
references.pmid: 12359667
references.citation: Synapse. 2005 Apr;56(1):1-11
references.pmid: 15700288
references.citation: J Neurosci. 2009 Feb 25;29(8):2344-54
references.pmid: 19244511
references.citation: Trends Neurosci. 1991 Jan;14(1):21-7
references.pmid: 1709528
references.citation: Neurosci Biobehav Rev. 2000 Jun;24(4):417-63
references.pmid: 10817843
references.citation: Trends Pharmacol Sci. 2005 May;26(5):237-43
references.pmid: 15860370
references.citation: Psychopharmacology (Berl). 2003 Jul;168(1-2):66-74
references.pmid: 12442201
references.citation: J Neurosci. 2010 Dec 15;30(50):17102-10
references.pmid: 21159980
references.citation: Schizophr Bull. 2005 Jul;31(3):672-96
references.pmid: 16020551
references.citation: Neuropharmacology. 2012 Mar;62(3):1574-83
references.pmid: 21277876
references.citation: PLoS One. 2011;6(11):e27187
references.pmid: 22073284
references.citation: Am J Addict. 2011 Jan-Feb;20(1):78-86
references.pmid: 21175924
references.citation: Pharmacol Biochem Behav. 2009 Sep;93(3):237-47
references.pmid: 19410598
references.citation: Cereb Cortex. 1999 Jan-Feb;9(1):20-6
references.pmid: 10022492
references.citation: Neuroimage. 1997 Jan;5(1):49-62
references.pmid: 9038284
references.citation: J Neurosci. 2012 Aug 8;32(32):10915-24
references.pmid: 22875926
references.citation: Exp Brain Res. 1989;75(3):457-69
references.pmid: 2744104
references.citation: Am J Psychiatry. 1991 May;148(5):621-6
references.pmid: 2018164
references.citation: Cereb Cortex. 2000 Nov;10(11):1078-92
references.pmid: 11053229
references.citation: J Neurosci. 2008 Nov 26;28(48):12691-9
references.pmid: 19036962
references.citation: Schizophr Bull. 2011 May;37(3):514-23
references.pmid: 21505118
references.citation: Nat Neurosci. 2010 Jan;13(1):76-83
references.pmid: 19915563
references.citation: Proc Natl Acad Sci U S A. 2004 May 25;101(21):8174-9
references.pmid: 15148381
references.citation: Neurosci Biobehav Rev. 2003 Jan-Mar;27(1-2):3-18
references.pmid: 12732219
references.citation: Neuropsychologia. 2011 Jun;49(7):1660-9
references.pmid: 21392517
references.citation: J Neuropsychiatry Clin Neurosci. 1999 Summer;11(3):361-9
references.pmid: 10440013
references.citation: J Physiol. 2012 Feb 15;590(4):669-81
references.pmid: 22250212
references.citation: Behav Brain Res. 2009 Dec 7;204(2):295-305
references.pmid: 19100784
references.citation: Nat Rev Neurosci. 2004 Oct;5(10):793-807
references.pmid: 15378039
references.citation: Nature. 1996 Oct 17;383(6601):621-4
references.pmid: 8857537
references.citation: Synapse. 2011 Apr;65(4):278-86
references.pmid: 20687106
references.citation: Am J Psychiatry. 2003 Jun;160(6):1041-52
references.pmid: 12777258
references.citation: Schizophr Res. 2003 Apr 1;60(2-3):285-98
references.pmid: 12591590
references.citation: J Neurosci. 2003 Nov 5;23(31):9987-95
references.pmid: 14602812
references.citation: Biol Psychiatry. 2003 Sep 1;54(5):504-14
references.pmid: 12946879
references.citation: J Comp Neurol. 1997 Oct 13;387(1):12-26
references.pmid: 9331168
references.citation: Cereb Cortex. 2001 May;11(5):430-40
references.pmid: 11313295
references.citation: Biol Psychiatry. 2011 Mar 1;69(5):432-41
references.pmid: 21146155
references.citation: Neurosci Biobehav Rev. 1999 Nov;23(7):993-1010
references.pmid: 10580313
references.citation: Science. 2007 Dec 7;318(5856):1645-7
references.pmid: 18063801
references.citation: Br J Psychiatry. 1988 May;152:641-8
references.pmid: 3262397
references.citation: Ann N Y Acad Sci. 2004 Jun;1021:148-59
references.pmid: 15251884
references.citation: Synapse. 2007 Oct;61(10):843-50
references.pmid: 17603809
references.citation: Biol Psychiatry. 2006 Sep 15;60(6):585-90
references.pmid: 16780812
references.citation: Synapse. 1992 Jul;11(3):184-90
references.pmid: 1636149
references.citation: Neuroscience. 1997 Oct;80(4):1149-58
references.pmid: 9284067
references.citation: Brain Struct Funct. 2014 Jan;219(1):395-406
references.pmid: 23400698
references.citation: J Neurosci. 2001 Aug 1;21(15):5824-31
references.pmid: 11466454
references.citation: Neuroscience. 2001;106(1):5-14
references.pmid: 11564412
references.citation: J Neurosci. 1997 Mar 1;17(5):1880-90
references.pmid: 9030646
references.citation: Biol Psychol. 2000 Oct;54(1-3):241-57
references.pmid: 11035225
references.citation: Am J Psychiatry. 1999 Jan;156(1):11-8
references.pmid: 9892292
references.citation: Neuroimage. 2003 Jul;19(3):1085-94
references.pmid: 12880834
references.citation: Behav Brain Res. 1988 Dec 1;31(2):193-8
references.pmid: 2849457
references.citation: Cereb Cortex. 2007 May;17(5):1235-40
references.pmid: 16818475
references.citation: Pharmacol Biochem Behav. 2007 Feb;86(2):189-99
references.pmid: 17222895
references.citation: Eur J Neurosci. 2011 May;33(9):1716-23
references.pmid: 21450043
references.citation: J Neurosci. 2000 Jan 1;20(1):485-94
references.pmid: 10627624
references.citation: J Exp Anal Behav. 2005 Nov;84(3):653-66
references.pmid: 16596984
references.citation: Proc Natl Acad Sci U S A. 2011 Jul 19;108(29):12131-6
references.pmid: 21730187
references.citation: J Neurosci. 2013 Mar 13;33(11):4913-22
references.pmid: 23486962
references.citation: Neuron. 2010 Sep 9;67(5):821-33
references.pmid: 20826313
references.citation: Philos Trans R Soc Lond B Biol Sci. 2008 Oct 12;363(1507):3257-66
references.pmid: 18640916
references.citation: Nat Neurosci. 2011 Dec 04;15(1):20-2
references.pmid: 22138646
references.citation: J Neurosci. 2004 Feb 18;24(7):1551-60
references.pmid: 14973230