[Abstract Title]. - Society for Neuroscience

Authors: *J. WANG 1 , S. CARNICELLA 1 , A. ZAPATA 2 , T. SHIPPENBERG 2 , D. RON 1,3 ;
1 Dept. of Neurol., Gallo Res. Ctr., Emeryville, CA; 2 Integrative Neurosci. Section, NIDA,
Baltimore, MD; 3 Dept. of Neurol., Univ. of California San Francisco, Emeryville, CA
Abstract: The ventral tegmental area (VTA) dopaminergic neurons play an essential role in
alcohol reward and addiction. Recently, we found that intra-VTA infusion of the Glial cell linederived
neurotrophic factor (GDNF) produced a very rapid attenuation of rat operant selfadministration
of alcohol (1). We hypothesized that the acute actions of GDNF in the VTA are
due to changes in neuronal activity. To address this hypothesis we used slice cell-attached
recording to examine whether GDNF alters the spontaneous firing of VTA neurons. We found
that application of GDNF, but not its heat-inactivated form, induced a rapid increase in the firing
frequency of Ih and tyrosine hydroxylase positive but not Ih negative neurons suggesting that
GDNF selectively increases dopaminergic neuron firing in the VTA. To explore a possible
mechanism underlying GDNF augmentation of firing, we used whole-cell current-clamp
recordings and showed that GDNF application caused a depolarization of membrane potential of
dopaminergic neurons. Enhancement of firing of VTA dopaminergic neurons may result in an
increase in dopamine release in the nucleus accumbens (NAc). We therefore used in vivo
microdialysis and observed an elevation in the level of dopamine in the NAc after infusion of
GDNF into the VTA. Together, our results suggest that GDNF acutely and selectively increases
the spontaneous firing of VTA dopaminergic neurons, which leads to an increase in dopamine
release in the NAc. This excitatory effect of GDNF on VTA neuronal activity may underlie the
mechanism by which GDNF in the VTA reduces alcohol consumption. 1. Carnicella et al. 2008
PNAS, In Press.
Disclosures: J. Wang, None; S. Carnicella, None; A. Zapata, None; T. Shippenberg,
None; D. Ron, None.
Poster
240. Intrinsic Membrane Properties: Modulation of Neuronal Firing Properties by Inputs
and Activity
Time: Sunday, November 16, 2008, 1:00 pm - 5:00 pm
Program#/Poster#: 240.4/E26
Topic: B.10.a. Neural oscillators
Support: INSERM
ANR