Elsevier

Neuroscience

Volume 137, Issue 3, 2006, Pages 727-735
Neuroscience

Behavioural neuroscience
Amphetamine induces dendritic growth in ventral tegmental area dopaminergic neurons in vivo via basic fibroblast growth factor

https://doi.org/10.1016/j.neuroscience.2005.09.038Get rights and content

Abstract

Dopaminergic neurons of the ventral tegmental area are implicated in the physiology of reward, and long-lasting changes in their function induced by exposure to psychostimulant drugs are related to the pathophysiology of drug abuse. It is not known, however, whether such changes are accompanied by morphological changes in these neurons. We characterized and labeled cells in slices containing the ventral tegmental area using whole-cell electrophysiological methods. Injections of saline or amphetamine were given to rats on postnatal days 10, 12 and 14 and individual neurons were examined one to four weeks later. We show that repeated exposure to amphetamine induces substantial dendritic growth of ventral tegmental area dopaminergic neurons in vivo. Furthermore, we show, by immuno-neutralization of endogenous basic fibroblast growth factor, that the amphetamine-induced increase in astrocytic basic fibroblast growth factor in the ventral tegmental area is essential for these morphological changes. We propose that the amphetamine-induced elaboration of the dendritic arbor of dopaminergic neurons leads to their increased excitability and contributes to compulsive drug-seeking and relapse.

Section snippets

Animals

Subjects were male Wistar rats, the progeny of timed-pregnant females (Charles River, St. Constant, QC, Canada). Litters were cross-fostered and culled at birth (six males, four females), and were weaned on postnatal day 21. Male rats were maintained on a normal light/dark cycle with food and water freely available in the home cage. All procedures conformed to the Canadian Council on Animal Care Guidelines and were approved by the Concordia University Animal Care Committee. All efforts were

Amphetamine induces dendritic growth in VTA dopaminergic neurons

We first examined whether early postnatal exposure to amphetamine alters the morphology of dopaminergic neurons in the paranigral subdivision of the VTA. These neurons send a dense projection to the nucleus accumbens (Swanson 1982, Fallon 1988) and have characteristically similar morphology (Phillipson, 1979). Rats were administered amphetamine (2.0mg/kg, s.c.) or saline on postnatal days 10, 12 and 14. On postnatal days 21 through 42, tissue slices containing the VTA were taken and examined

Discussion

The present study demonstrates that repeated early postnatal exposure to amphetamine induces long-lasting alterations in the dendritic morphology of dopaminergic neurons in the paranigral subdivision VTA. The somatodendritic region of these neurons is where psychostimulant drugs, such as amphetamine, act to initiate the long-lasting changes that underlie enhanced behavioral and neurochemical responses to the effects of these drugs (Vezina 2004, Kalivas and Stewart 1991). Furthermore, the

Acknowledgments

Research was supported by Canadian Institutes of Health Research (J.S.), Fonds de recherche sur la nature et les technologies (J.S. and C.A.C.), Canada Foundation for Innovation (C.A.C.) and Natural Sciences and Engineering Research Council of Canada (NSERC; C.A.C.). D.M. was supported by a pre-doctoral scholarship from NSERC. We thank S. Amir for helpful comments on an earlier version of the manuscript.

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