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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2000-8-24
pubmed:abstractText
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 (> or =0.09 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 alpha-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 (> or =0.09 mg/kg).
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0022-3565
pubmed:author
pubmed:issnType
Print
pubmed:volume
294
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
458-65
pubmed:dateRevised
2003-11-14
pubmed:meshHeading
pubmed-meshheading:10900219-2-Amino-5-phosphonovalerate, pubmed-meshheading:10900219-6-Cyano-7-nitroquinoxaline-2,3-dione, pubmed-meshheading:10900219-Animals, pubmed-meshheading:10900219-Dopamine, pubmed-meshheading:10900219-Dose-Response Relationship, Drug, pubmed-meshheading:10900219-Excitatory Amino Acid Antagonists, pubmed-meshheading:10900219-Glutamic Acid, pubmed-meshheading:10900219-Male, pubmed-meshheading:10900219-Microdialysis, pubmed-meshheading:10900219-Nicotine, pubmed-meshheading:10900219-Nicotinic Agonists, pubmed-meshheading:10900219-Nucleus Accumbens, pubmed-meshheading:10900219-Pipecolic Acids, pubmed-meshheading:10900219-Rats, pubmed-meshheading:10900219-Rats, Sprague-Dawley, pubmed-meshheading:10900219-Receptors, AMPA, pubmed-meshheading:10900219-Receptors, N-Methyl-D-Aspartate, pubmed-meshheading:10900219-Stimulation, Chemical, pubmed-meshheading:10900219-Ventral Tegmental Area
pubmed:year
2000
pubmed:articleTitle
Systemic nicotine stimulates dopamine release in nucleus accumbens: re-evaluation of the role of N-methyl-D-aspartate receptors in the ventral tegmental area.
pubmed:affiliation
Department of Pharmacology, Health Science Center, University of Tennessee, Memphis 38163, USA.
pubmed:publicationType
Journal Article