caa a22 4500 463185935 CHVBK 20180406164853.0 cr unu---uuuuu 170326e20070201xx s 000 0 eng 10.1007/s00726-006-0316-z doi (NATIONALLICENCE)springer-10.1007/s00726-006-0316-z Combined administration of PHCCC, a positive allosteric modulator of mGlu4 receptors and ACPT-I, mGlu III receptor agonist evokes antidepressant-like effects in rats [Elektronische Daten] [K. Kłak, A. Pałucha, P. Brański, M. Sowa, A. Pilc] Summary.: Numerous pharmacological data indicate involvement of glutamate, the major excitatory neurotransmitter in the brain, in the pathophysiology of several neuropsychiatric disorders. It was shown in the preclinical studies that compounds which can reduce the excess of glutamate release (for example group III metabotropic receptors agonists) possess potential therapeutic properties. Thus we focused our interests on (−)-N-phenyl-7-(hydroxyimino) cyclopropa[b]chromen-1a-carboxamide (PHCCC), which is a positive allosteric modulator of mGlu4 receptor. We examined the potential antidepressant-like activity of PHCCC after injection into the brain ventricles alone, or together with (1S,3R,4S)-1-aminocyclo-pentane-1,3,4-tricarboxylic acid (ACPT-I), a nonselective group III mGlu receptor agonist, using the forced swimming test (FST) in rats. We found that ACPT-I induced a dose dependent antidepressant-like effect in FST, which was blocked by an antagonist of group III mGlu receptors (RS)-alpha-cyclopropyl-4-phosphonophenylglycine (CPPG). PHCCC injected intracerebroventricular was not effective, however when the compound was administered together with non-effective dose of ACPT-I, a profound antidepressant-like activity in FST was demonstrated. This effect was reversed by CPPG, group III mGlu receptors antagonist. Results of our studies indicate that a combined administration positive allosteric modulation of mGlu4 receptor and agonists of group III mGlu receptors may be a promising target in the future treatment of depressive disorder. Springer-Verlag, 2006 Keywords: Depression - Antidepressant activity - Group III mGlu receptors - PHCCC - ACPT-I nationallicence Kłak K. Department of Neurobiology, Institute of Pharmacology, Polish Academy of Sciences, Kraków, Poland aut Pałucha A. Department of Neurobiology, Institute of Pharmacology, Polish Academy of Sciences, Kraków, Poland aut Brański P. Department of Neurobiology, Institute of Pharmacology, Polish Academy of Sciences, Kraków, Poland aut Sowa M. Department of Neurobiology, Institute of Pharmacology, Polish Academy of Sciences, Kraków, Poland aut Pilc A. Department of Neurobiology, Institute of Pharmacology, Polish Academy of Sciences, Kraków, Poland aut Amino Acids Springer-Verlag 32/2(2007-02-01), 169-172 0939-4451 32:2<169 2007 32 726 https://doi.org/10.1007/s00726-006-0316-z text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s00726-006-0316-z text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Kłak K. Department of Neurobiology, Institute of Pharmacology, Polish Academy of Sciences, Kraków, Poland aut NATIONALLICENCE 700 1- Pałucha A. Department of Neurobiology, Institute of Pharmacology, Polish Academy of Sciences, Kraków, Poland aut NATIONALLICENCE 700 1- Brański P. Department of Neurobiology, Institute of Pharmacology, Polish Academy of Sciences, Kraków, Poland aut NATIONALLICENCE 700 1- Sowa M. Department of Neurobiology, Institute of Pharmacology, Polish Academy of Sciences, Kraków, Poland aut NATIONALLICENCE 700 1- Pilc A. Department of Neurobiology, Institute of Pharmacology, Polish Academy of Sciences, Kraków, Poland aut NATIONALLICENCE 773 0- Amino Acids Springer-Verlag 32/2(2007-02-01), 169-172 0939-4451 32:2<169 2007 32 726 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer