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Antidepressant-like effect of ethanol in mice forced swimming test is mediated via inhibition of NMDA/nitric oxide/cGMP signaling pathway.
- Source :
-
Alcohol . May2021, Vol. 92, p53-63. 11p. - Publication Year :
- 2021
-
Abstract
- There is evidence for a dramatic relationship between depression and alcohol consumption. Depressed patients may abuse ethanol because this agent reduces the symptoms of depression. In the current study, we aimed to investigate the NMDA/nitric oxide/cGMP pathway in the antidepressant-like effect of ethanol in an animal model of behavioral despair. Animals were subjected to locomotor activity in an open-field test separately, followed by a forced swimming test. During the forced swimming test (FST), ethanol (2 and 2.5 g/kg) significantly decreased the immobility time without altering the locomotor activity of animals. The antidepressant-like effect of ethanol (2.5 g/kg) was reversed by co-administration of N-methyl-D-aspartate (NMDA, 75 mg/kg), L-arginine (750 mg/kg), or sildenafil (5 mg/kg). In contrast, co-administration of MK-801 (0.05 mg/kg), ketamine (1 mg/kg), and ifenprodil (0.5 mg/kg) as antagonists of NMDAR, and NG-nitro-L-arginine methyl ester (L-NAME, 10 mg/kg), 7-nitroindazole (7-NI, 30 mg/kg), and methylene blue (10 mg/kg) as inhibitors of nitric oxide synthase (NOS), or 1H-[1,2,4]oxadiazole[4,3-a]quinoxalin-1-one (ODQ) (20 mg/kg), a nitric oxide/cyclic-guanosine monophosphate (NO-cGMP) inhibitor, with a subeffective dose of ethanol (1.5 g/kg), significantly decreased the immobility time in the FST. Furthermore, injection of ethanol 2.5 g/kg alone or 1.5 g/kg with a 7-NI subeffective dose, significantly decreased the nitrite levels in the hippocampus and prefrontal cortex. Hence, it is concluded that blockade of NMDA receptors and the nitric oxide/cyclic-guanosine monophosphate (NO-cGMP) pathway might be involved in the antidepressant-like effect of ethanol in mice. [ABSTRACT FROM AUTHOR]
- Subjects :
- *NITRIC oxide
*DESPAIR
*NITRIC-oxide synthases
*KETAMINE abuse
*ETHANOL
*SWIMMING
*METHYLENE blue
*ANTIDEPRESSANTS
*RESEARCH
*ANIMAL experimentation
*RESEARCH methodology
*ARGININE
*CELL receptors
*MEDICAL cooperation
*EVALUATION research
*NUCLEOTIDES
*CELLULAR signal transduction
*COMPARATIVE studies
*MENTAL depression
*MICE
*ASPARTIC acid
*PHARMACODYNAMICS
Subjects
Details
- Language :
- English
- ISSN :
- 07418329
- Volume :
- 92
- Database :
- Academic Search Index
- Journal :
- Alcohol
- Publication Type :
- Academic Journal
- Accession number :
- 149615327
- Full Text :
- https://doi.org/10.1016/j.alcohol.2021.01.005