Potential antidepressant-like effect of piperazine derivative LQFM212 in mice: Role of monoaminergic pathway and brain-derived neurotrophic factor
| Autor: | Adriane Ferreira de Brito, Ricardo Menegatti, Dayane Moreira da Silva, Lorrane Kelle da Silva Moreira, Pablinny Moreira Galdino de Carvalho, Elson Alves Costa, Paulo César Ghedini, Lorrayne Siqueira, Daiany Priscilla Bueno da Silva, Carina Sofia Cardoso, Iziara Ferreira Florentino |
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| Rok vydání: | 2020 |
| Předmět: |
Male
Pharmacology Serotonergic Piperazines 03 medical and health sciences Behavioral Neuroscience AMPT Mice 0302 clinical medicine Monoaminergic medicine Prazosin Animals Biogenic Monoamines 030304 developmental biology Brain-derived neurotrophic factor 0303 health sciences Neurotransmitter Agents Behavior Animal business.industry Depression Brain-Derived Neurotrophic Factor Antidepressive Agents Disease Models Animal Monoamine neurotransmitter business Sulpiride 030217 neurology & neurosurgery Behavioural despair test medicine.drug Signal Transduction |
| Zdroj: | Behavioural brain research. 401 |
| ISSN: | 1872-7549 |
| Popis: | Major depression disorder (MDD) is one of the most widespread and debilitating psychiatric diseases and may be associated with other mental disorders such as anxiety. Despite advances in neurobiology studies, currently no established mechanism can explain all facets of MDD, and available drugs often show therapeutic delay for clinical effectiveness and response rates in patients are around 50 %. Previous activities of piperazine derivatives on CNS are indicators of its therapeutic potential for treating mental disorders. In this regard, we have previously shown that the piperazine derivative 2,6-di-tert-butyl-4-((4-(2-hydroxyethyl)piperazin-1-yl)methyl)phenol (LQFM212) has anxiolytic-like activity which involves serotonergic pathway, nicotinic receptors and BZD-site of GABAA receptor, without cognitive impairments. Herein, was evaluated the potential antidepressant-like effect of LQFM212 on forced swimming test (FST) after a single dose of 54 μmol/kg and after repeated treatment for 15 days in mice. Pretreatment with WAY-100635, PCPA, prazosin, SCH-23390, sulpiride or AMPT reversed the antidepressant-like effect on FST, suggesting that monoaminergic pathway contributes for effects of LQFM212. Furthermore, repeated treatment with LQFM212 increased hippocampal BDNF levels dosed by ELISA kit. In assessment of possible adverse effects, repeated treatment with LQFM212 did not alter the body weight of the animals, glutathione levels in the liver, and serum levels of AST, ALT, urea, and creatinine. Taken together, the results showed that LQFM212 has an antidepressant-like effect that involves monoaminergic pathway and increased BDNF levels. This compound represents promising candidate for prototype of psychoactive drugs for treatment of anxiety and depression disorders since these pathological conditions may exist in comorbidities. |
| Databáze: | OpenAIRE |
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