The Hepatocyte Growth Factor/c-Met Antagonist, Divalinal-Angiotensin IV, Blocks the Acquisition of Methamphetamine Dependent Conditioned Place Preference in Rats

Brain Sciences

John W. Wright¹  Wendy L. Wilson³  Vanessa Wakeling¹  Alan S. Boydstun²  Audrey Jensen¹  Leen Kawas⁴ 

[1] Department of Psychology, Washington State University, Pullman, WA 99164-4820, USA;L-3 Communications, Link Simulation and Training, Wright Patterson Air Force Base, OH 45433-7955, USA;Department of Psychology, Dickinson State University, Dickinson, ND 58601, USA;Program in Pharmacology and Toxicology, Washington State University, Pullman, WA 99164-6510, USA;

关键词: methamphetamine;    conditioned place preference;    divalinal-angiotensin IV;    AT₄ receptor subtype;    hepatocyte growth factor;    c-Met receptor;   

DOI  :  10.3390/brainsci2030298

来源: mdpi

【 摘 要 】

The use of methamphetamine (MA) is increasing in the U.S. and elsewhere around the world. MA’s capacity to cause addiction significantly exceeds other psychostimulant drugs, and its use negatively impacts learning and memory. Recently, attempts have been made to interfere with the presumed mechanism(s) underlying the establishment of drug-induced memory consolidation. The majority of these studies have employed matrix metalloproteinase (MMP) inhibitors to disrupt MMP-induced extracellular matrix molecule dependent synaptic reconfiguration, or GABA receptor agonists. The present investigation utilized an angiotensin IV (AngIV) analogue, Divalinal-AngIV (divalinal), to disrupt acquisition of MA-induced dependence in rats as measured using the conditioned place preference paradigm. Results indicate that both acute and chronic intracerebroventricular infusion of divalinal prior to each daily subcutaneous injection of MA prevented acquisition. However, divalinal was unable to prevent MA-induced reinstatement after prior acquisition followed by extinction trials. These results indicate that prevention of MA dependence can be accomplished by blockade of the brain AT₄ receptor subtype. On the other hand, once MA-induced memory consolidation is in place divalinal appears to be ineffective. Mechanistic studies indicated that divalinal is a potent inhibitor of the hepatocyte growth factor (HGF)/c-Met receptor system, and thus it appears that a functional HGF/c-Met system is required for the acquisition of MA-mediated conditioned place preference.

【 授权许可】

CC BY   
© 2012 by the authors; licensee MDPI, Basel, Switzerland.