Systemic nicotine stimulates dopamine release in nucleus accumbens

Re- evaluation of the role of N-methyl-D-aspartate receptors in the ventral tegmental area

Yitong Fu, Shannon G. Matta, Wenqing Gao, Victoria G. Brower, Burt Sharp

Research output: Contribution to journalArticle

111 Citations (Scopus)

Abstract

Systemic nicotine stimulates dopamine (DA) release in the nucleus accumbens (NAcc), and N-methyl-D-aspartate (NMDA) receptors in the ventral tegmental area (VTA) appear to be involved. However, it is not known whether the secretion of DA elicited by nicotine depends on the tonic and/or phasic activation of NMDA receptors by glutamate (Glu). To clarify this, in vivo microdialysis was conducted in freely moving, alert rats to measure DA and Glu overflows in the NAcc and Glu in the VTA. Nicotine (0.065, 0.09, or 0.135 mg/kg delivered i.v. at 0.09 mg/kg/60 s via a jugular cannula) dose dependently stimulated NAcc DA secretion (P < .05). However, 0.065 mg/kg nicotine failed to stimulate Glu release in the VTA, whereas higher doses of nicotine (γ0.09 mg/kg) were effective (P < .05). Administering the competitive NMDA receptor antagonists, 2-amino-5-phosphonopentanoic acid (AP- 5; 1 mM) or 0.2 mM cis-4-phosphonomethyl-2-piperidine carboxylic acid (CGS 19755) through the VTA probe, abolished NAcc DA release after 0.065 mg/kg nicotine (P < .01) and reduced the response to 0.09 mg/kg nicotine. Therefore, the NAcc DA response to a relatively low dose of nicotine depends on the tonic activation of NMDA receptors in the VTA. In contrast, infusing 1 mM 2-amino-5-phosphonopentanoic acid or 1 mM 6-cyano-7-nitroquinoxaline-2,3- dione (CNQX), an α-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) receptor antagonist, into the NAcc through the microdialysis probe had no effect on NAcc DA secretion in response to 0.09 mg/kg nicotine. These findings, coupled with data showing that Glu secretion in the VTA was stimulated only by higher doses of nicotine, indicate that the phasic release of VTA Glu is involved in the NAcc DA response to higher doses of nicotine (≥0.09 mg/kg).

Original languageEnglish (US)
Pages (from-to)458-465
Number of pages8
JournalJournal of Pharmacology and Experimental Therapeutics
Volume294
Issue number2
StatePublished - Aug 2000

Fingerprint

Ventral Tegmental Area
Nucleus Accumbens
N-Methyl-D-Aspartate Receptors
Nicotine
Dopamine
Glutamic Acid
2-Amino-5-phosphonovalerate
selfotel
Microdialysis
6-Cyano-7-nitroquinoxaline-2,3-dione
Transcription Factor AP-1
Propionates
Carboxylic Acids
Neck

All Science Journal Classification (ASJC) codes

  • Pharmacology

Cite this

Systemic nicotine stimulates dopamine release in nucleus accumbens : Re- evaluation of the role of N-methyl-D-aspartate receptors in the ventral tegmental area. / Fu, Yitong; Matta, Shannon G.; Gao, Wenqing; Brower, Victoria G.; Sharp, Burt.

In: Journal of Pharmacology and Experimental Therapeutics, Vol. 294, No. 2, 08.2000, p. 458-465.

Research output: Contribution to journalArticle

@article{8d80893635624b83997d9ef8846685f1,
title = "Systemic nicotine stimulates dopamine release in nucleus accumbens: Re- evaluation of the role of N-methyl-D-aspartate receptors in the ventral tegmental area",
abstract = "Systemic nicotine stimulates dopamine (DA) release in the nucleus accumbens (NAcc), and N-methyl-D-aspartate (NMDA) receptors in the ventral tegmental area (VTA) appear to be involved. However, it is not known whether the secretion of DA elicited by nicotine depends on the tonic and/or phasic activation of NMDA receptors by glutamate (Glu). To clarify this, in vivo microdialysis was conducted in freely moving, alert rats to measure DA and Glu overflows in the NAcc and Glu in the VTA. Nicotine (0.065, 0.09, or 0.135 mg/kg delivered i.v. at 0.09 mg/kg/60 s via a jugular cannula) dose dependently stimulated NAcc DA secretion (P < .05). However, 0.065 mg/kg nicotine failed to stimulate Glu release in the VTA, whereas higher doses of nicotine (γ0.09 mg/kg) were effective (P < .05). Administering the competitive NMDA receptor antagonists, 2-amino-5-phosphonopentanoic acid (AP- 5; 1 mM) or 0.2 mM cis-4-phosphonomethyl-2-piperidine carboxylic acid (CGS 19755) through the VTA probe, abolished NAcc DA release after 0.065 mg/kg nicotine (P < .01) and reduced the response to 0.09 mg/kg nicotine. Therefore, the NAcc DA response to a relatively low dose of nicotine depends on the tonic activation of NMDA receptors in the VTA. In contrast, infusing 1 mM 2-amino-5-phosphonopentanoic acid or 1 mM 6-cyano-7-nitroquinoxaline-2,3- dione (CNQX), an α-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) receptor antagonist, into the NAcc through the microdialysis probe had no effect on NAcc DA secretion in response to 0.09 mg/kg nicotine. These findings, coupled with data showing that Glu secretion in the VTA was stimulated only by higher doses of nicotine, indicate that the phasic release of VTA Glu is involved in the NAcc DA response to higher doses of nicotine (≥0.09 mg/kg).",
author = "Yitong Fu and Matta, {Shannon G.} and Wenqing Gao and Brower, {Victoria G.} and Burt Sharp",
year = "2000",
month = "8",
language = "English (US)",
volume = "294",
pages = "458--465",
journal = "Journal of Pharmacology and Experimental Therapeutics",
issn = "0022-3565",
publisher = "American Society for Pharmacology and Experimental Therapeutics",
number = "2",

}

TY - JOUR

T1 - Systemic nicotine stimulates dopamine release in nucleus accumbens

T2 - Re- evaluation of the role of N-methyl-D-aspartate receptors in the ventral tegmental area

AU - Fu, Yitong

AU - Matta, Shannon G.

AU - Gao, Wenqing

AU - Brower, Victoria G.

AU - Sharp, Burt

PY - 2000/8

Y1 - 2000/8

N2 - Systemic nicotine stimulates dopamine (DA) release in the nucleus accumbens (NAcc), and N-methyl-D-aspartate (NMDA) receptors in the ventral tegmental area (VTA) appear to be involved. However, it is not known whether the secretion of DA elicited by nicotine depends on the tonic and/or phasic activation of NMDA receptors by glutamate (Glu). To clarify this, in vivo microdialysis was conducted in freely moving, alert rats to measure DA and Glu overflows in the NAcc and Glu in the VTA. Nicotine (0.065, 0.09, or 0.135 mg/kg delivered i.v. at 0.09 mg/kg/60 s via a jugular cannula) dose dependently stimulated NAcc DA secretion (P < .05). However, 0.065 mg/kg nicotine failed to stimulate Glu release in the VTA, whereas higher doses of nicotine (γ0.09 mg/kg) were effective (P < .05). Administering the competitive NMDA receptor antagonists, 2-amino-5-phosphonopentanoic acid (AP- 5; 1 mM) or 0.2 mM cis-4-phosphonomethyl-2-piperidine carboxylic acid (CGS 19755) through the VTA probe, abolished NAcc DA release after 0.065 mg/kg nicotine (P < .01) and reduced the response to 0.09 mg/kg nicotine. Therefore, the NAcc DA response to a relatively low dose of nicotine depends on the tonic activation of NMDA receptors in the VTA. In contrast, infusing 1 mM 2-amino-5-phosphonopentanoic acid or 1 mM 6-cyano-7-nitroquinoxaline-2,3- dione (CNQX), an α-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) receptor antagonist, into the NAcc through the microdialysis probe had no effect on NAcc DA secretion in response to 0.09 mg/kg nicotine. These findings, coupled with data showing that Glu secretion in the VTA was stimulated only by higher doses of nicotine, indicate that the phasic release of VTA Glu is involved in the NAcc DA response to higher doses of nicotine (≥0.09 mg/kg).

AB - Systemic nicotine stimulates dopamine (DA) release in the nucleus accumbens (NAcc), and N-methyl-D-aspartate (NMDA) receptors in the ventral tegmental area (VTA) appear to be involved. However, it is not known whether the secretion of DA elicited by nicotine depends on the tonic and/or phasic activation of NMDA receptors by glutamate (Glu). To clarify this, in vivo microdialysis was conducted in freely moving, alert rats to measure DA and Glu overflows in the NAcc and Glu in the VTA. Nicotine (0.065, 0.09, or 0.135 mg/kg delivered i.v. at 0.09 mg/kg/60 s via a jugular cannula) dose dependently stimulated NAcc DA secretion (P < .05). However, 0.065 mg/kg nicotine failed to stimulate Glu release in the VTA, whereas higher doses of nicotine (γ0.09 mg/kg) were effective (P < .05). Administering the competitive NMDA receptor antagonists, 2-amino-5-phosphonopentanoic acid (AP- 5; 1 mM) or 0.2 mM cis-4-phosphonomethyl-2-piperidine carboxylic acid (CGS 19755) through the VTA probe, abolished NAcc DA release after 0.065 mg/kg nicotine (P < .01) and reduced the response to 0.09 mg/kg nicotine. Therefore, the NAcc DA response to a relatively low dose of nicotine depends on the tonic activation of NMDA receptors in the VTA. In contrast, infusing 1 mM 2-amino-5-phosphonopentanoic acid or 1 mM 6-cyano-7-nitroquinoxaline-2,3- dione (CNQX), an α-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) receptor antagonist, into the NAcc through the microdialysis probe had no effect on NAcc DA secretion in response to 0.09 mg/kg nicotine. These findings, coupled with data showing that Glu secretion in the VTA was stimulated only by higher doses of nicotine, indicate that the phasic release of VTA Glu is involved in the NAcc DA response to higher doses of nicotine (≥0.09 mg/kg).

UR - http://www.scopus.com/inward/record.url?scp=0033942236&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0033942236&partnerID=8YFLogxK

M3 - Article

VL - 294

SP - 458

EP - 465

JO - Journal of Pharmacology and Experimental Therapeutics

JF - Journal of Pharmacology and Experimental Therapeutics

SN - 0022-3565

IS - 2

ER -