title: Nicotine stimulation of extracellular glutamate levels in the nucleus accumbens: neuropharmacological characterization.
abstract: In the present study, we have characterized the neuropharmacological regulation of nicotine-induced increases in extracellular nucleus accumbens glutamate levels. Sprague-Dawley rats were stereotaxically implanted with 2 mm microdialysis probes in the nucleus accumbens and on the following day in vivo microdialysis experiments were performed in awake, freely moving animals. An acute dose of nicotine (0.3-0.6 mg/kg, s.c.) produced an increase in nucleus accumbens glutamate levels with a maximal increase of approximately 50% following the higher dose. No changes in nucleus accumbens aspartate levels were found. The increase in glutamate levels following nicotine (0.3 mg/kg, s.c.) was blocked by mecamylamine (1 mg/kg, i.p. ) but not by haloperidol (0.2 mg/kg, i.p.) pretreatment. Local perfusion of artificial cerebrospinal fluid (CSF) without calcium did not alter nicotine (0.3 mg/kg, s.c.) stimulation of glutamate levels. Local perfusion with a selective blocker for the GLT-1 glutamate transporter, dihydrokainic acid (DHKA) (10(-4) M), had no effect, while local perfusion with a nonselective glutamate transporter blocker, L-trans-pyrrolidine-2,4-dicarboxylic acid (PDC) (10(-4) M), blocked nicotine (0.3 mg/kg, s.c.) stimulation of glutamate levels. In animals previously dopamine denervated by local injections of 6-hydroxydopamine (6-OHDA) into the nucleus accumbens, nicotine (0.3 mg/kg, s.c.) stimulation of glutamate levels was enhanced vs. sham-lesioned animals. These findings demonstrate a novel form of nucleus accumbens glutamate release that is dopamine- and calcium-independent. The ability of PDC to block the effects of nicotine suggest that a glutamate transporter may be involved in mediating the stimulation of glutamate release.
authors.affiliation: New York University, Department of Psychiatry, Veteran's Affairs Medical Center, New York, New York, USA. REID.MALCOLM_S+@NEW-YORK.VA.GOV
authors.forename: M S
authors.initials: MS
authors.lastname: Reid
authors.forename: L
authors.initials: L
authors.lastname: Fox
authors.forename: L B
authors.initials: LB
authors.lastname: Ho
authors.forename: S P
authors.initials: SP
authors.lastname: Berger
mesh_terms: D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D018528:ATP-Binding Cassette Transporters / Q000037:antagonists & inhibitors; D027322:Amino Acid Transport System X-AG; D000818:Animals; D001224:Aspartic Acid / Q000378:metabolism; D001692:Biological Transport; D003714:Denervation; D003998:Dicarboxylic Acids / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism; D005110:Extracellular Space / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism*; D006220:Haloperidol / Q000494:pharmacology; D007608:Kainic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D008464:Mecamylamine / Q000494:pharmacology; D017551:Microdialysis; D014179:Neurotransmitter Uptake Inhibitors / Q000494:pharmacology; D009538:Nicotine / Q000494:pharmacology*; D009714:Nucleus Accumbens / Q000187:drug effects / Q000502:physiology*; D016627:Oxidopamine / Q000494:pharmacology; D011759:Pyrrolidines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D018528:ATP-Binding Cassette Transporters; D027322:Amino Acid Transport System X-AG; D003998:Dicarboxylic Acids; D014179:Neurotransmitter Uptake Inhibitors; D011759:Pyrrolidines; D015102:3,4-Dihydroxyphenylacetic Acid; D001224:Aspartic Acid; D018698:Glutamic Acid; C020889:dihydrokainic acid; D008464:Mecamylamine; D009538:Nicotine; D016627:Oxidopamine; C083486:pyrrolidine-2,4-dicarboxylic acid; D006220:Haloperidol; D007608:Kainic Acid; D004298:Dopamine