Fluoxetine reverses the behavioral despair induced by neurogenic stress in mice: role of N-methyl-d-aspartate and opioid receptors

• Published in: Canadian journal of physiology and pharmacology 2016-06, Vol.94 (6), p.599-612
• Main Authors: Haj-Mirzaian, Arya, Kordjazy, Nastaran, Ostadhadi, Sattar, Amiri, Shayan, Haj-Mirzaian, Arvin, Dehpour, AhmadReza
• Format: Article
• Language: English
• Subjects: acute foot shock stress; Animals; Antidepressive Agents, Second-Generation - therapeutic use; depression; Depression - drug therapy; Depression - etiology; Depression - psychology; Despair; Dizocilpine Maleate - pharmacology; Dosage and administration; Drug therapy; Fluoxetine; Fluoxetine - therapeutic use; fluoxétine; Health aspects; Ion channels; Male; Mice; Neuropsychology; NMDA receptor; opioid receptor; Opioids; Physiological psychology; Psychopharmacology; Receptors; Receptors, N-Methyl-D-Aspartate - antagonists & inhibitors; Receptors, N-Methyl-D-Aspartate - physiology; Receptors, Opioid - physiology; Rodents; récepteur du NMDA; récepteur d’opioïdes; stress causé par un choc électrique aigu aux pattes; Stress response; Stress, Psychological - complications; Stress, Psychological - drug therapy; Stress, Psychological - psychology
• ISSN: 0008-4212; 1205-7541
• DOI: 10.1139/cjpp-2015-0429

Opioid and N-methyl- d -aspartate (NMDA) receptors mediate different effects of fluoxetine. We investigated whether opioid and NMDA receptors are involved in the protective effect of fluoxetine against the behavioral despair induced by acute physical stress in male mice. We used the forced swimming test (FST), tail suspension test (TST), and open-field test (OFT) for behavioral evaluation. We used fluoxetine, naltrexone (opioid receptor antagonist), MK-801 (NMDA receptor antagonist), morphine (opioid receptor agonist), and NMDA (NMDA receptor agonist). Acute foot-shock stress (FSS) significantly induced behavioral despair (depressive-like) and anxiety-like behaviors in tests. Fluoxetine (5 mg/kg) reversed the depressant-like effect of FSS, but it did not alter the locomotion and anxiety-like behavior in animals. Acute administration of subeffective doses of naltrexone (0.3 mg/kg) or MK-801 (0.01 mg/kg) potentiated the antidepressant-like effect of fluoxetine, while subeffective doses of morphine (1 mg/kg) and NMDA (75 mg/kg) abolished this effect of fluoxetine. Also, co-administration of subeffective doses of naltrexone (0.05 mg/kg) and MK-801 (0.003 mg/kg) with fluoxetine (1 mg/kg) induced a significant decrease in the immobility time in FST and TST. Our results showed that opioid and NMDA receptors (alone or in combination) are involved in the antidepressant-like effect of fluoxetine against physical stress.