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Brain Sci. 2012, 2(3), 298-318; doi:10.3390/brainsci2030298
Article

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

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Received: 9 May 2012; in revised form: 6 July 2012 / Accepted: 10 August 2012 / Published: 20 August 2012
(This article belongs to the Special Issue Addiction and Neuroadaptation)
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Abstract: 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.
Keywords: methamphetamine; conditioned place preference; divalinal-angiotensin IV; AT4 receptor subtype; hepatocyte growth factor; c-Met receptor methamphetamine; conditioned place preference; divalinal-angiotensin IV; AT4 receptor subtype; hepatocyte growth factor; c-Met receptor
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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MDPI and ACS Style

Wright, J.W.; Wilson, W.L.; Wakeling, V.; Boydstun, A.S.; Jensen, A.; Kawas, L.; Harding, J.W. The Hepatocyte Growth Factor/c-Met Antagonist, Divalinal-Angiotensin IV, Blocks the Acquisition of Methamphetamine Dependent Conditioned Place Preference in Rats. Brain Sci. 2012, 2, 298-318.

AMA Style

Wright JW, Wilson WL, Wakeling V, Boydstun AS, Jensen A, Kawas L, Harding JW. The Hepatocyte Growth Factor/c-Met Antagonist, Divalinal-Angiotensin IV, Blocks the Acquisition of Methamphetamine Dependent Conditioned Place Preference in Rats. Brain Sciences. 2012; 2(3):298-318.

Chicago/Turabian Style

Wright, John W.; Wilson, Wendy L.; Wakeling, Vanessa; Boydstun, Alan S.; Jensen, Audrey; Kawas, Leen; Harding, Joseph W. 2012. "The Hepatocyte Growth Factor/c-Met Antagonist, Divalinal-Angiotensin IV, Blocks the Acquisition of Methamphetamine Dependent Conditioned Place Preference in Rats." Brain Sci. 2, no. 3: 298-318.



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