Antidepressant-like effect of aripiprazole via 5-HT1A, D1, and D2 receptors in the prefrontal cortex of olfactory bulbectomized mice

• Published in: Journal of pharmacological sciences Vol. 137; no. 3; pp. 241 - 247
• Main Authors: Takahashi, Kohei, Nakagawasai, Osamu, Nemoto, Wataru, Odaira, Takayo, Sakuma, Wakana, Tan-No, Koichi
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 01.07.2018
• Subjects: 5-HT1A receptor; Antidepressant; Aripiprazole; Dopamine receptors; Olfactory bulbectomy; Antidepressant; Aripiprazole; Olfactory bulbectomy; 5-HT1A receptor; Dopamine receptors
• ISSN: 1347-8613; 1347-8648
• DOI: 10.1016/j.jphs.2018.06.006

Olfactory bulbectomized (OBX) mice exhibit depressive-like behaviors and memory deficits. We have reported that aripiprazole (ARI) ameliorates the behavioral hyper-responsivity to dopamine agonists and memory deficits in OBX mice; however, it is unclear whether ARI affects OBX-induced depressive-like behavior. To address this question, we evaluated the effect of ARI on depressive-like behavior in OBX mice using the forced swim test (FST). In addition, we investigated the effect of ARI on c-Fos expression in the prefrontal cortex (PFC), striatum, and hippocampus of OBX mice using western blotting. OBX mice exhibited a longer immobility duration in the FST 14 days after surgery. Depressive-like behavior in OBX mice was reversed 30 min after administration of ARI (0.01 or 0.03 mg/kg). In addition, c-Fos expression was increased in the PFC, but not the striatum or hippocampus, 30 min after acute administration of ARI. These effects were inhibited by administration of the selective 5-HT1A, D1, and D2 receptor antagonists, WAY100635, SCH23390, and L-741,626, respectively. These findings suggest that ARI produces an antidepressant effect in OBX mice that may be mediated by 5-HT1A, D1, and D2 receptors in the PFC.