title: Serotonergic and noradrenergic systems are implicated in the antidepressant-like effect of ursolic acid in mice.
abstract: Ursolic acid (UA) is a natural pentacyclic triterpenoid carboxylic acid that exerts antidepressant-like effects in the tail suspension test (TST) and in the forced swimming test, and this effect was reported to be mediated by the dopaminergic system. Many studies show that currently available antidepressant agents have effects on multiple neurotransmitter systems which account for their efficacy. Therefore, this study was aimed at investigating the possible involvement of the serotonergic, noradrenergic, glutamatergic and opioid systems in the antidepressant-like effect of UA. To this end, several pharmacological agents were administered to verify their ability to influence the antidepressant-like responses elicited by UA in the TST in mice. The open-field test was used to assess the locomotor activity. The results show that the pre-treatment of mice with ρ-chlorophenylalanine (100mg/kg, i.p., 4 days) or α-methyl-ρ-tyrosine (100mg/kg, i.p.) but not with N-methyl-d-aspartate (0.1 pmol/mouse, i.c.v.) or naloxone (1mg/kg, i.p.), was able to prevent the antidepressant-like effect of UA (0.1mg/kg, p.o.). Sub-effective doses of fluoxetine (5mg/kg, p.o.) or reboxetine (2mg/kg, p.o.), but not ketamine (0.1mg/kg, i.p.) or MK-801 (0.001 mg/kg, p.o.), was capable of potentiating the effect of a sub-effective dose of UA (0.001 mg/kg, p.o.) in the TST. None of the treatments affected locomotor activity. Altogether, the results show an involvement of the serotonergic and noradrenergic systems, but not the glutamatergic or opioid systems, in the antidepressant-like effect of UA.
authors.affiliation: Department of Biochemistry, Center of Biological Sciences, Universidade Federal de Santa Catarina, Campus Universitário - Trindade, 88040-900 Florianópolis, SC, Brazil.
authors.forename: André R S
authors.initials: AR
authors.lastname: Colla
authors.affiliation: Department of Biochemistry, Center of Biological Sciences, Universidade Federal de Santa Catarina, Campus Universitário - Trindade, 88040-900 Florianópolis, SC, Brazil.
authors.forename: Agatha
authors.initials: A
authors.lastname: Oliveira
authors.affiliation: Department of Biochemistry, Center of Biological Sciences, Universidade Federal de Santa Catarina, Campus Universitário - Trindade, 88040-900 Florianópolis, SC, Brazil.
authors.forename: Francis L
authors.initials: FL
authors.lastname: Pazini
authors.affiliation: Department of Biochemistry, Center of Biological Sciences, Universidade Federal de Santa Catarina, Campus Universitário - Trindade, 88040-900 Florianópolis, SC, Brazil.
authors.forename: Julia M
authors.initials: JM
authors.lastname: Rosa
authors.affiliation: Department of Biochemistry, Center of Biological Sciences, Universidade Federal de Santa Catarina, Campus Universitário - Trindade, 88040-900 Florianópolis, SC, Brazil.
authors.forename: Luana M
authors.initials: LM
authors.lastname: Manosso
authors.affiliation: Department of Biochemistry, Center of Biological Sciences, Universidade Federal de Santa Catarina, Campus Universitário - Trindade, 88040-900 Florianópolis, SC, Brazil.
authors.forename: Mauricio P
authors.initials: MP
authors.lastname: Cunha
authors.affiliation: Department of Biochemistry, Center of Biological Sciences, Universidade Federal de Santa Catarina, Campus Universitário - Trindade, 88040-900 Florianópolis, SC, Brazil. Electronic address: alsrodri@gmail.com.
authors.forename: Ana Lúcia S
authors.initials: AL
authors.lastname: Rodrigues
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D005260:Female; D007276:Injections, Intraventricular; D008297:Male; D051379:Mice; D009638:Norepinephrine / Q000502:physiology*; D012701:Serotonin / Q000502:physiology*; D014315:Triterpenes / Q000008:administration & dosage / Q000494:pharmacology*; D000097245:Ursolic Acid
chemical_list: D000928:Antidepressive Agents; D009638:Norepinephrine; D012701:Serotonin; D014315:Triterpenes; D000097245:Ursolic Acid
keywords: Antidepressant; Monoaminergic system; Tail suspension test; Ursolic acid