Piromelatine ameliorates memory deficits associated with chronic mild stress-induced anhedonia in rats.
Psychopharmacology (Berl)
; 233(12): 2229-39, 2016 06.
Article
en En
| MEDLINE
| ID: mdl-27007604
ABSTRACT
RATIONALE Previous studies have demonstrated that piromelatine (a melatonin and serotonin 5-HT1A and 5-HT1D agonist) exerts an antidepressant activity in rodent models of acute stress and improves cognitive impairments in a rat model of Alzheimer's disease (AD). However, the role of piromelatine in chronic stress-induced memory dysfunction remains unclear. OBJECTIVE:
The aim of this study was to determine whether piromelatine ameliorates chronic mild stress (CMS)-induced memory deficits and explore the underlying mechanisms.METHODS:
Rats were exposed randomly to chronic mild stressors for 7 weeks to induce anhedonia (reflected by a significant decrease in sucrose intake), which was used to select rats vulnerable (CMS-anhedonic, CMSA) or resistant (CMS-resistant, CMSR) to stress. Piromelatine (50 mg/kg) was administered daily during the last 2 weeks of CMS. The tail suspension and forced swimming tests were adopted to further characterize vulnerable and resilient rats. The Y-maze and novel object recognition (NOR) tests were used to evaluate memory performance. Brain-derived neurotrophic factor (BDNF), cAMP response element-binding protein (CREB), phosphorylated CREB (pCREB), and cytogenesis were measured in the hippocampus.RESULTS:
We found that only CMSA rats displayed significant increases in immobility time in the tail suspension and forced swimming tests; memory deficits in the Y-maze and NOR tests; significant decreases in hippocampal BDNF, CREB, and pCREB expression; and cytogenesis. All these anhedonia-associated effects were reversed by piromelatine.CONCLUSIONS:
Piromelatine ameliorates memory deficits associated with CMS-induced anhedonia in rats and this effect may be mediated by restoring hippocampal BDNF, CREB, and cytogenesis deficits.Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Piranos
/
Estrés Psicológico
/
Anhedonia
/
Indoles
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Trastornos de la Memoria
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Antidepresivos
Tipo de estudio:
Etiology_studies
/
Prognostic_studies
/
Risk_factors_studies
Límite:
Animals
Idioma:
En
Revista:
Psychopharmacology (Berl)
Año:
2016
Tipo del documento:
Article