Ms. Reid et al., Nicotine stimulation of extracellular glutamate levels in the nucleus accumbens: Neuropharmacological characterization, SYNAPSE, 35(2), 2000, pp. 129-136
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.