RT Journal Article
SR Electronic
T1 Brain-Derived Neurotrophic Factor Signaling Modulates Cocaine Induction of Reward-Associated Ultrasonic Vocalization in Rats
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 463
OP 468
DO 10.1124/jpet.109.158535
VO 332
IS 2
A1 Stacey N. Williams
A1 Ashiwel S. Undieh
YR 2010
UL http://jpet.aspetjournals.org/content/332/2/463.abstract
AB Cocaine exhibits high liability for inducing addictive behaviors, but the mechanisms of neuroplasticity underlying the behavioral effects remain unclear. As a crucial mediator of neuroplasticity in diverse functional models, brain-derived neurotrophic factor (BDNF) could contribute to the mechanisms of addiction-related neuroplasticity. Here, we addressed the hypothesis that cocaine increases synaptic dopamine, which induces BDNF protein expression to initiate addiction-related behavior in the rat. An enzyme-linked immunosorbent assay was used to measure BDNF protein expression in rat striatal tissues. For behavioral readout, we used a noninvasive measurement system to measure the emission of 50-kHz ultrasonic vocalization (USV), a response that correlates with electrical brain stimulation and conditioned place preference behavior in rodents. A single injection of cocaine significantly increased BDNF protein expression, but this effect was not further augmented by repeated cocaine administration. A single administration of cocaine elicited significant and dose-related USV responses, and the magnitude of the behavior increased with repeated drug administration. R-(+)-7-Chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine (SCH23390), but not raclopride, significantly attenuated cocaine-induced BDNF protein expression, whereas either the D1-like or D2-like receptor antagonist blocked cocaine-induced USV behavior. Furthermore, significant USV behavior was elicited by the nonselective dopamine agonist, apomorphine, but not by agonists that are selective for D1-like or D2-like receptors. Intracerebroventricular injection of the neurotrophin TrkB receptor inhibitor, K252a, blocked cocaine-induced USV behavior but not locomotor activity. These results suggest that neurotrophin signaling downstream of dopamine receptor function probably constitutes a crucial link in cocaine induction of USV behavior and may contribute to the mechanisms underlying the development of addiction-related behaviors. Copyright © 2010 by The American Society for Pharmacology and Experimental Therapeutics