Metabotropic Glutamate Receptor 7 (Mglur7) Allosteric Agonist, AMN082 Attenuates the Acquisition and Expression of Cocaine-Induced Behavioral Sensitization in Mice

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Metabotropic Glutamate Receptor 7 (Mglur7) Allosteric Agonist, AMN082 Attenuates the Acquisition and Expression of Cocaine-Induced Behavioral Sensitization in Mice

tally new view on RAS system has been proposed. In ACE2-AT-(1-7) – receptor Mas axis may become this concept, RAS system is divided into two contra- in the future an important therapeutic target in cardio- dictory systems, dependent on ACE/ACE2 balance: vascular diseases as well as in metabolic diseases. ACE-AT II-AT1 receptor vs. ACE2-AT-(1-7) – Mas Therefore, a new therapeutic challenge has been es- receptor. tablished for pharmacology: creation of drugs which Drugs which influence RAS axis, perhaps not only “stimulate” ACE2 – AT-(1-7) – Mas receptor axis. inhibit the production and action of AT II, but also ac- AVE 0991, nonpeptide agonist of receptor for tivate the “alternative”, beneficial route which ends in AT-(1-7), might be one of such drugs. AT-(1-7) production. Metabotropic glutamate receptor 7 (mGluR7) allosteric agonist, AMN082 attenuates the acquisition and expression of cocaine-induced behavioral sensitization in mice Ma³gorzata Jenda, Kinga Gawe³, Jolanta H. Kotliñska Department of Pharmacology and Pharmacodynamics, Medical University, ChodŸki 4a, PL 20-093 Lublin, Poland Behavioral sensitization to locomotor stimulant ef- ment mice were challenged with cocaine (10 mg/kg, fects of psychostimulants is defined as a progressive ip). To assess the influence of AMN082 on the acqui- increase in the effect of these drugs, following their sition of cocaine sensitization, this drug was adminis- repeated (intermittent) administration. Neuronal tered 30 min before each of the five cocaine injections changes underlying this phenomenon are thought to during development of sensitization. The influence of contribute to development of compulsive drug seek- AMN082 on the expression of sensitization was esti- ing and craving that characterize addiction. Glutamate mated by a single injection of this drug prior the chal- transmission has been implicated in regulating the lenge dose of cocaine. Our studies revealed that psychopharmacologic effects of cocaine [Schmidt and AMN082 at the doses of 2.5 and 5 mg/kg, ip blocked Pierce, Ann NY Acad Sci, 2010]. The aim of the pres- acquisition and expression of sensitization to locomo- ent study was to evaluate the influence of meta- tor stimulant effect of cocaine. Moreover, the botropic glutamate receptors 7 (mGluR7) allosteric mGluR7 allosteric antagonist, MMPIP (10 mg/kg, ip) agonist, AMN082 on the development and expression reversed the AMN082-induced effects. These results of cocaine-induced locomotor sensitization in mice. support the relevance of the mGluR7 in the motiva- Behavioral sensitization was induced by five intrape- tional effect of cocaine and development of cocaine- ritoneal (ip) injections of cocaine at the dose of seeking behavior. 10 mg/kg every 3 days. Four days after the last treat- 50 Pharmacological Reports, 2013, 65, suppl..

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