title: Potential antidepressant-like properties of the TC G-1008, a GPR39 (zinc receptor) agonist.
abstract: Some forms of depression appear to be more related to the glutamatergic system. G-coupled protein receptor 39 (GPR39) is the metabotropic zinc receptor, which may be involved in the pathophysiology of depression and in the antidepressant response. Its deficiency abolishes the antidepressant response, which means that GPR39 is required to obtain a therapeutic effect in depression. This raises the possibility that agonists of the zinc receptor may have a role in antidepressant treatment. To explore this possibility we investigated animal behaviour in the forced swim test, the tail suspension test (to assess antidepressant-like properties), the light/dark test and the elevated plus maze test (to assess anxiolytic-like properties), following acute administration of a GPR39 agonist (TC G-1008). We found an antidepressant response (as measured by the forced swim test but not by the tail suspension test) in mice following the GPR39 agonist treatment. Additionally, we observed the opposite results in the light/dark box (decreased overall distance; increased time spent in the lit compartment; decreased time spent in the dark compartment; increased freezing time) and elevated plus maze (no significant changes), which may be a consequence of the sedative effect of TC G-1008. We also found hippocampal GPR39 and brain-derived neurotrophic factor (BDNF) up-regulation following administration of the GPR39 agonist, which may be undiscovered so far as a possible novel agent in the treatment of mood disorders.
authors.affiliation: Department of Pharmacobiology, Jagiellonian University Medical College, Medyczna 9, PL 30-688 Krakow, Poland. Electronic address: katarzyna.mlyniec@uj.edu.pl.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Młyniec
authors.affiliation: Department of Pharmacobiology, Jagiellonian University Medical College, Medyczna 9, PL 30-688 Krakow, Poland.
authors.forename: Gabriela
authors.initials: G
authors.lastname: Starowicz
authors.affiliation: Department of Radioligands, Jagiellonian University Medical College, Medyczna 9, PL 30-688 Krakow, Poland.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Gaweł
authors.affiliation: Department of Radioligands, Jagiellonian University Medical College, Medyczna 9, PL 30-688 Krakow, Poland.
authors.forename: Ewelina
authors.initials: E
authors.lastname: Frąckiewicz
authors.affiliation: Department of Pharmacobiology, Jagiellonian University Medical College, Medyczna 9, PL 30-688 Krakow, Poland; Institute of Pharmacology, Polish Academy of Sciences, Smętna 12, PL 31-343 Krakow, Poland.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Nowak
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects*; D015153:Blotting, Western; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D003866:Depressive Disorder / Q000188:drug therapy; D004195:Disease Models, Animal; D006624:Hippocampus / Q000378:metabolism; D007274:Injections, Intraperitoneal; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D011743:Pyrimidines / Q000494:pharmacology*; D043562:Receptors, G-Protein-Coupled / Q000819:agonists* / Q000378:metabolism; D013312:Stress, Physiological / Q000187:drug effects; D013449:Sulfonamides / Q000494:pharmacology*; D013550:Swimming; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D000928:Antidepressive Agents; D019208:Brain-Derived Neurotrophic Factor; C512928:GPR39 protein, mouse; C000621962:GPR39-C3; D011743:Pyrimidines; D043562:Receptors, G-Protein-Coupled; D013449:Sulfonamides
keywords: Agonist; Antidepressants; Depression; GPR39; TC-G 1008; Zinc