title: Intravenous nicotine injection induces rapid, experience-dependent sensitization of glutamate release in the ventral tegmental area and nucleus accumbens.
abstract: Although numerous data suggest that glutamate (GLU) is involved in mediating the neural effects of nicotine, direct data on nicotine-induced changes in GLU release are still lacking. Here, we used high-speed amperometry with enzyme-based GLU and enzyme-free GLU-null biosensors to examine changes in extracellular GLU levels in the ventral tegmental area (VTA) and nucleus accumbens shell (NAcc) induced by intravenous nicotine in a low, behaviorally active dose (30 μg/kg) in freely moving rats. Using this approach, we found that the initial nicotine injection in drug-naive conditions induces rapid, transient, and relatively small GLU release (~ 90 nM; latency ~ 15 s, duration ~ 60 s) that is correlative in the VTA and NAcc. Following subsequent nicotine injections within the same session, this phasic GLU release was supplemented by stronger tonic increases in GLU levels (100-300 nM) that paralleled increases in drug-induced locomotor activation. GLU responses induced by repeated nicotine injections were more phasic and stronger in the NAcc than in VTA. Therefore, GLU is phasically released within the brain's reinforcement circuit following intravenous nicotine administration. Robust enhancement of nicotine-induced GLU responses following repeated injections suggests this change as an important mediator of sensitized behavioral and neural effects of nicotine. By using high-speed amperometry with glutamate (GLU) biosensors, we show that i.v. nicotine at a low, behaviorally relevant dose induces rapid GLU release in the NAcc and VTA that is enhanced following repeated drug injections. This is the first study reporting second-scale fluctuations in extracellular GLU levels induced by nicotine in two critical structures of the motivation-reinforcement circuit and rapid sensitization of GLU responses coupled with locomotor sensitization.
authors.affiliation: In-Vivo Electrophysiology Unit, Behavioral Neuroscience Branch, National Institute on Drug Abuse - Intramural Research Program, National Institutes of Health, DHHS, Baltimore, Maryland, USA.
authors.forename: Magalie
authors.initials: M
authors.lastname: Lenoir
authors.forename: Eugene A
authors.initials: EA
authors.lastname: Kiyatkin
mesh_terms: D000818:Animals; D015374:Biosensing Techniques; D004305:Dose-Response Relationship, Drug; D005973:Glutamine / Q000378:metabolism*; D007275:Injections, Intravenous; D008124:Locomotion / Q000187:drug effects; D008297:Male; D009538:Nicotine / Q000008:administration & dosage / Q000494:pharmacology*; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D020318:Rats, Long-Evans; D017557:Ventral Tegmental Area / Q000187:drug effects* / Q000378:metabolism
chemical_list: D005973:Glutamine; D009538:Nicotine
keywords: electrochemistry; enzyme-based glutamate biosensors; experience-dependent neuroplasticity of glutamate neurotransmission; glutamate release
references.citation: Naunyn Schmiedebergs Arch Pharmacol. 1994 May;349(5):443-6
references.pmid: 8065457
references.citation: Brain Res. 1994 Oct 3;659(1-2):117-25
references.pmid: 7820652
references.citation: Trends Pharmacol Sci. 1990 Nov;11(11):462-8
references.pmid: 1980041
references.citation: Neuroscience. 1998 Aug;85(4):1285-309
references.pmid: 9681963
references.citation: Synapse. 2002 Mar 15;43(4):227-37
references.pmid: 11835517
references.citation: Acta Physiol Scand. 1970 Oct;80(2):222-34
references.pmid: 5475342
references.citation: Prog Neuropsychopharmacol Biol Psychiatry. 2001 Jan;25(1):59-71
references.pmid: 11263759
references.citation: ACS Chem Neurosci. 2013 May 15;4(5):652-65
references.pmid: 23448428
references.citation: J Pharmacol Sci. 2003 Oct;93(2):143-8
references.pmid: 14578581
references.citation: Amino Acids. 1998;14(1-3):51-6
references.pmid: 9871441
references.citation: J Neurophysiol. 2012 Jul;108(1):285-99
references.pmid: 22496525
references.citation: Biochem J. 1969 Dec;115(5):889-96
references.pmid: 5360723
references.citation: Psychopharmacology (Berl). 2010 May;209(4):383-94
references.pmid: 20232056
references.citation: Adv Pharmacol. 1998;42:737-40
references.pmid: 9328004
references.citation: J Pharmacol Exp Ther. 2000 Aug;294(2):458-65
references.pmid: 10900219
references.citation: Psychopharmacology (Berl). 1995 Dec;122(4):390-94
references.pmid: 8657839
references.citation: Pain. 1982 Mar;12(3):259-264
references.pmid: 7078986
references.citation: Br J Pharmacol. 1984 Sep;83(1):49-55
references.pmid: 6487896
references.citation: Neuropsychopharmacology. 2009 Jan;34(2):266-81
references.pmid: 18418357
references.citation: Psychopharmacology (Berl). 1997 Mar;130(1):28-40
references.pmid: 9089846
references.citation: Brain Res. 1999 Mar 20;822(1-2):88-106
references.pmid: 10082887
references.citation: Eur J Pharmacol. 2000 Mar 30;393(1-3):295-314
references.pmid: 10771025
references.citation: Ciba Found Symp. 1990;152:153-62; discussion 162-8
references.pmid: 2209252
references.citation: J Addict Res Ther. 2011 Apr 20;S1(1):
references.pmid: 22454789
references.citation: Psychopharmacology (Berl). 2002 Jun;161(4):370-8
references.pmid: 12073164
references.citation: J Neurosci. 2013 Jun 12;33(24):9937-49
references.pmid: 23761889
references.citation: Proc Natl Acad Sci U S A. 2010 Mar 16;107(11):5190-5
references.pmid: 20212132
references.citation: Eur J Pharmacol. 2003 Oct 31;479(1-3):237-47
references.pmid: 14612154
references.citation: Neuropharmacology. 2005;49 Suppl 1:167-78
references.pmid: 16023685
references.citation: Neurochem Res. 2002 Mar;27(3):253-61
references.pmid: 11958525
references.citation: J Neurosci. 2007 May 23;27(21):5730-43
references.pmid: 17522317
references.citation: J Neurophysiol. 2007 Dec;98(6):3388-96
references.pmid: 17942622
references.citation: Neuropharmacology. 2011 Dec;61(8):1399-405
references.pmid: 21896278
references.citation: J Mol Neurosci. 2010 Jan;40(1-2):154-63
references.pmid: 19669944
references.citation: Neuropsychopharmacology. 2011 Sep;36(10):2125-38
references.pmid: 21654739
references.citation: PLoS One. 2011;6(11):e26501
references.pmid: 22069455
references.citation: Respir Physiol. 1996 Dec;106(3):231-8
references.pmid: 9017841
references.citation: Prog Neuropsychopharmacol Biol Psychiatry. 2007 Nov 15;31(8):1625-38
references.pmid: 17936462
references.citation: Brain Res. 2011 Apr 6;1383:141-53
references.pmid: 21295014
references.citation: Am J Physiol. 1996 Jun;270(6 Pt 1):C1807-14
references.pmid: 8764165
references.citation: Br J Pharmacol. 2010 Jun;160(4):785-809
references.pmid: 20136842
references.citation: Front Syst Neurosci. 2011 Nov 24;5:94
references.pmid: 22275885
references.citation: Mol Pharmacol. 2012 Apr;81(4):541-8
references.pmid: 22222765
references.citation: Pharmacology. 1995 Feb;50(2):128-36
references.pmid: 7716176
references.citation: Psychol Rev. 1987 Oct;94(4):469-92
references.pmid: 3317472
references.citation: Pharmacol Biochem Behav. 1998 Apr;59(4):1021-30
references.pmid: 9586863
references.citation: Naunyn Schmiedebergs Arch Pharmacol. 1975;288(1):29-56
references.pmid: 1099463