Amphetamine induces dendritic growth in ventral tegmental area dopaminergic neurons in vivo via basic fibroblast growth factor.
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.
Mueller
D
D
Center for Studies in Behavioral Neurobiology (SP-244), Department of Psychology, Concordia University, 7141 Sherbrooke Street West, Montreal, Quebec, Canada H4B 1R6.
Chapman
C A
CA
Stewart
J
J
D000661:Amphetamine / Q000494:pharmacology*; D000818:Animals; D003712:Dendrites / Q000187:drug effects* / Q000648:ultrastructure; D004298:Dopamine / Q000502:physiology*; D018492:Dopamine Antagonists / Q000494:pharmacology; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D004594:Electrophysiology; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D007150:Immunohistochemistry; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure; D018408:Patch-Clamp Techniques; D019257:Quinpirole / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism; D017557:Ventral Tegmental Area / Q000166:cytology* / Q000187:drug effects
D018492:Dopamine Antagonists; D018765:Dopamine Uptake Inhibitors; D016222:Fibroblast Growth Factor 2; D019257:Quinpirole; D000661:Amphetamine; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine