The Hepatocyte Growth Factor/c-Met Antagonist, Divalinal-Angiotensin IV, Blocks the Acquisition of Methamphetamine Dependent Conditioned Place Preference in Rats
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...
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| Format: | Article |
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MDPI AG
2012-08-01
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| Series: | Brain Sciences |
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| Online Access: | http://www.mdpi.com/2076-3425/2/3/298 |
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| author | Alan S. Boydstun Joseph W. Harding Leen Kawas Audrey Jensen Wendy L. Wilson Vanessa Wakeling John W. Wright |
| author_facet | Alan S. Boydstun Joseph W. Harding Leen Kawas Audrey Jensen Wendy L. Wilson Vanessa Wakeling John W. Wright |
| author_sort | Alan S. Boydstun |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-19T18:17:01Z |
| format | Article |
| id | doaj.art-eb230728dc4743659991e545e642f5b3 |
| institution | Directory Open Access Journal |
| issn | 2076-3425 |
| language | English |
| last_indexed | 2024-12-19T18:17:01Z |
| publishDate | 2012-08-01 |
| publisher | MDPI AG |
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| series | Brain Sciences |
| spelling | doaj.art-eb230728dc4743659991e545e642f5b32022-12-21T20:11:05ZengMDPI AGBrain Sciences2076-34252012-08-012329831810.3390/brainsci2030298The Hepatocyte Growth Factor/c-Met Antagonist, Divalinal-Angiotensin IV, Blocks the Acquisition of Methamphetamine Dependent Conditioned Place Preference in RatsAlan S. BoydstunJoseph W. HardingLeen KawasAudrey JensenWendy L. WilsonVanessa WakelingJohn W. WrightThe 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.http://www.mdpi.com/2076-3425/2/3/298methamphetamineconditioned place preferencedivalinal-angiotensin IVAT4 receptor subtypehepatocyte growth factorc-Met receptor |
| spellingShingle | Alan S. Boydstun Joseph W. Harding Leen Kawas Audrey Jensen Wendy L. Wilson Vanessa Wakeling John W. Wright The Hepatocyte Growth Factor/c-Met Antagonist, Divalinal-Angiotensin IV, Blocks the Acquisition of Methamphetamine Dependent Conditioned Place Preference in Rats Brain Sciences methamphetamine conditioned place preference divalinal-angiotensin IV AT4 receptor subtype hepatocyte growth factor c-Met receptor |
| title | The Hepatocyte Growth Factor/c-Met Antagonist, Divalinal-Angiotensin IV, Blocks the Acquisition of Methamphetamine Dependent Conditioned Place Preference in Rats |
| title_full | The Hepatocyte Growth Factor/c-Met Antagonist, Divalinal-Angiotensin IV, Blocks the Acquisition of Methamphetamine Dependent Conditioned Place Preference in Rats |
| title_fullStr | The Hepatocyte Growth Factor/c-Met Antagonist, Divalinal-Angiotensin IV, Blocks the Acquisition of Methamphetamine Dependent Conditioned Place Preference in Rats |
| title_full_unstemmed | The Hepatocyte Growth Factor/c-Met Antagonist, Divalinal-Angiotensin IV, Blocks the Acquisition of Methamphetamine Dependent Conditioned Place Preference in Rats |
| title_short | The Hepatocyte Growth Factor/c-Met Antagonist, Divalinal-Angiotensin IV, Blocks the Acquisition of Methamphetamine Dependent Conditioned Place Preference in Rats |
| title_sort | hepatocyte growth factor c met antagonist divalinal angiotensin iv blocks the acquisition of methamphetamine dependent conditioned place preference in rats |
| topic | methamphetamine conditioned place preference divalinal-angiotensin IV AT4 receptor subtype hepatocyte growth factor c-Met receptor |
| url | http://www.mdpi.com/2076-3425/2/3/298 |
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