Nicotine stimulation of extracellular glutamate levels in the nucleus accumbens: Neuropharmacological characterization

Citation
Ms. Reid et al., Nicotine stimulation of extracellular glutamate levels in the nucleus accumbens: Neuropharmacological characterization, SYNAPSE, 35(2), 2000, pp. 129-136
Citations number
60
Categorie Soggetti
Neurosciences & Behavoir
Journal title
SYNAPSE
ISSN journal
08874476 → ACNP
Volume
35
Issue
2
Year of publication
2000
Pages
129 - 136
Database
ISI
SICI code
0887-4476(200002)35:2<129:NSOEGL>2.0.ZU;2-A
Abstract
In the present study, we have characterized the neuropharmacological regula tion of nicotine-induced increases in extracellular nucleus accumbens gluta mate levels. Sprague-Dawley rats were stereotaxically implanted with 2 mm m icrodialysis probes in the nucleus accumbens and on the following day in vi vo 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 n ucleus accumbens glutamate levels with a maximal increase of approximately 50% following the higher dose. No changes in nucleus accumbens aspartate le vels were found. The increase in glutamate levels following nicotine (0.3 m g/kg, s.c.) was blocked by mecamylamine (1 mg/kg, i.p.) but not by haloperi dol (0.2 mg/kg, i.p.) pretreatment. Local perfusion of artificial cerebrosp inal fluid (CSF) without calcium did not alter nicotine (0.3 mg/kg, s.c.) s timulation of glutamate levels. Local perfusion with a selective blocker fo r the GLT-1 glutamate transporter, dihydrokainic acid (DHKA) (10(-4) M), ha d no effect, while local perfusion with a nonselective glutamate transporte r blocker, L-trans-pyrrolidine-2,4-dicarboxylic acid (PDC) (10(-4) M), bloc ked 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 de monstrate a novel form of nucleus accumbens glutamate release that is dopam ine- and calcium-independent. The ability of PDC to block the effects of ni cotine suggest that a glutamate transporter may be involved in mediating th e stimulation of glutamate release. (C) 2000 Wiley-Liss, Inc.