PT  - JOURNAL ARTICLE
AU  - Stacey N. Williams
AU  - Ashiwel S. Undieh
TI  - Brain-derived neurotrophic factor signaling modulates cocaine induction of reward-associated ultrasonic vocalization in rats
AID  - 10.1124/jpet.109.158535
DP  - 2009 Jan 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - jpet.109.158535
4099  - http://jpet.aspetjournals.org/content/early/2009/10/20/jpet.109.158535.short
4100  - http://jpet.aspetjournals.org/content/early/2009/10/20/jpet.109.158535.full
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. Enzyme-linked immunosorbent assay was used to measure BDNF protein expression in rat striatal tissues. For behavioral readout, we used the Metris Sonotrack 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. 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.The American Society for Pharmacology and Experimental Therapeutics