title: Neurobehavioral and genotoxic parameters of duloxetine in mice using the inhibitory avoidance task and comet assay as experimental models.
abstract: Duloxetine is a potent inhibitor of serotonin and noradrenaline reuptake, with weak effects on dopamine reuptake, used in the treatment of major depression. It has been recognized that some antidepressants can affect memory in humans, but there is not study that report the duloxetine effect on memory using the inhibitory avoidance. The aim of this work was to investigate the effect of duloxetine on short- and long-term memory (STM and LTM) in the inhibitory avoidance task in mice. Duloxetine (10 and 20 mg/kg; i.p.) administered before or after the inhibitory avoidance training was not able to produce effects on STM e LTM (p>0.05). The group that received MK-801 (0.0625 mg/kg), an NMDA receptor antagonist, showed an impairment in STM and LTM (p<0.01). These effects were not reversed by duloxetine administration (p=0.114 and p=0.06, respectively). Duloxetine effect on memory 5 days after i.p. administration was also investigated. After this treatment both duloxetine doses used were unable to affect STM or LTM in the inhibitory avoidance task (p=0.371 and p=0.807, respectively). DNA damages were evaluated in brain tissues and blood by the comet assay, after subacute treatment (10 or 20 mg/kg by 5 days). Duloxetine did not induce genotoxic effects. However, when the cells were treated ex vivo hydrogen peroxide, a pro-oxidant effect on brain tissue from treated animals was observed with significantly higher DNA damage in comparison to untreated animals, suggesting increased susceptibility to injuries by reactive oxygen species in brain after treatment with duloxetine. Duloxetine did not produce any effect on memory after acute and subacute administration, suggesting that this antidepressant does not affect either memory acquisition or consolidation.
authors.affiliation: Curso de Pós-Graduação em Genética e Toxicologia Aplicada, Universidade Luterana do Brasil, Bairro São José, Canoas, RS, Brazil. patipere@yahoo.com.br
authors.forename: Patrícia
authors.initials: P
authors.lastname: Pereira
authors.forename: Janaína
authors.initials: J
authors.lastname: Gianesini
authors.forename: Cibele
authors.initials: C
authors.lastname: da Silva Barbosa
authors.forename: Graziela Freitas
authors.initials: GF
authors.lastname: Cassol
authors.forename: Rafael Gomes
authors.initials: RG
authors.lastname: Von Borowski
authors.forename: Vivian Francília Silva
authors.initials: VF
authors.lastname: Kahl
authors.forename: Shandale Emanuele
authors.initials: SE
authors.lastname: Cappelari
authors.forename: Jaqueline Nascimento
authors.initials: JN
authors.lastname: Picada
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D001362:Avoidance Learning / Q000187:drug effects*; D020552:Comet Assay; D004249:DNA Damage; D000068736:Duloxetine Hydrochloride; D008297:Male; D008568:Memory / Q000187:drug effects; D051379:Mice; D013876:Thiophenes / Q000494:pharmacology* / Q000633:toxicity*
chemical_list: D000928:Antidepressive Agents; D013876:Thiophenes; D000068736:Duloxetine Hydrochloride