Antidepressant-like effect of ethanol in mice forced swimming test is mediated via inhibition of NMDA/nitric oxide/cGMP signaling pathway

• Published in: Alcohol (Fayetteville, N.Y.) N.Y.), 2021-05, Vol.92, p.53-63
• Main Authors: Khan, Muhammad Imran, Nikoui, Vahid, Naveed, Aamir, Mumtaz, Faiza, Zaman, Hamid, Haider, Adnan, Aman, Waqar, Wahab, Abdul, Khan, Shahid Niaz, Ullah, Najeeb, Dehpour, Ahmad Reza
• Format: Article
• Language: English
• Subjects: Abuse; Alcohol; Alcohol use; Animal models; Antagonists; Antidepressants; Arginine; Behavioral despair; Cyclic GMP; depression; Dizocilpine; Drug dosages; Ethanol; forced swimming test (FST); Glutamic acid receptors; Glutamic acid receptors (ionotropic); Investigations; Ketamine; Locomotor activity; Mental depression; Methylene blue; mice; N-Methyl-D-aspartic acid receptors; NG-Nitroarginine methyl ester; Nitric oxide; nitric oxide cyclic-guanosine monophosphate (NO-cGMP); Nitric-oxide synthase; NMDA; Open-field behavior; Prefrontal cortex; Rodents; Signal transduction; Sildenafil
• ISSN: 0741-8329; 1873-6823
• DOI: 10.1016/j.alcohol.2021.01.005

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. [Display omitted] •Acute alcohol has an antidepressant-like effect in mice.•Alcohol inhibits NMDA in hippocampus and cortex.•Alcohol inhibits the NMDA/NO/cGMP pathway.