Intravenous nicotine injection induces rapid, experience-dependent sensitization of glutamate release in the ventral tegmental area and nucleus accumbens

Magalie Lenoir, Eugene A. Kiyatkin
J. Neurochem.. 2013-10-21; 127(4): 541-551
DOI: 10.1111/jnc.12450

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Although numerous data suggest that glutamate (GLU) is involved in mediating the
neural effects of nicotine, direct data on nicotine-induced changes in GLU
release are still lacking. Here, we used high-speed amperometry with enzyme-based
GLU and enzyme-free GLU-null biosensors to examine changes in extracellular GLU
levels in the ventral tegmental area (VTA) and nucleus accumbens shell (NAcc)
induced by intravenous nicotine in a low, behaviorally active dose (30 μg/kg) in
freely moving rats. Using this approach, we found that the initial nicotine
injection in drug-naive conditions induces rapid, transient, and relatively small
GLU release (~ 90 nM; latency ~ 15 s, duration ~ 60 s) that is correlative in the
VTA and NAcc. Following subsequent nicotine injections within the same session,
this phasic GLU release was supplemented by stronger tonic increases in GLU
levels (100-300 nM) that paralleled increases in drug-induced locomotor
activation. GLU responses induced by repeated nicotine injections were more
phasic and stronger in the NAcc than in VTA. Therefore, GLU is phasically
released within the brain’s reinforcement circuit following intravenous nicotine
administration. Robust enhancement of nicotine-induced GLU responses following
repeated injections suggests this change as an important mediator of sensitized
behavioral and neural effects of nicotine. By using high-speed amperometry with
glutamate (GLU) biosensors, we show that i.v. nicotine at a low, behaviorally
relevant dose induces rapid GLU release in the NAcc and VTA that is enhanced
following repeated drug injections. This is the first study reporting
second-scale fluctuations in extracellular GLU levels induced by nicotine in two
critical structures of the motivation-reinforcement circuit and rapid
sensitization of GLU responses coupled with locomotor sensitization.

Published 2013. This article is a U.S. Government work and is in the public domain in the USA.


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