Intrahippocampal administration of neurosteroid agmatine exhibits antinociceptive effect in neuropathic rat model: Modulation by sigma‐1 receptor

Depressed patients consuming reboxetine for therapeutic purpose also consume caffeine in the form tea or coffee drinks as a part of their daily life. Augmentation of caffeine having dopaminergic activity with reboxetine as an antidepressant agent may induce a positive effect in depression treatment. We screened this new augmentation approach consisting caffeine with reboxetine in mice using forced swim test and tail suspension test. Immobility parameter was estimated in six groups. Both drugs were dissolved in normal saline solution separately and injected (intra-peritoneal) in a volume of 10 ml/kg of body weight of animal. In forced swim test, drugs were administered 1 h prior to test session, whereas 30 min prior to test session in tail suspension test. Group I served as vehicle-treated (normal saline) control group. Group II and III received caffeine (10 mg/kg), and reboxetine 10 mg/kg, respectively, whereas Group IV, V, and VI received caffeine (2.5 mg/kg) + reboxetine (7.5 mg/kg), caffeine (5 mg/kg) + reboxetine (5 mg/kg), caffeine (7.5 mg/kg) + reboxetine (2.5 mg/kg) combinations, respectively. Groups II to VI were compared with Group I. In addition, Groups IV to VI were compared with Group III. Group II to VI showed a highly significant decrease in duration of immobility than Group I in both animal models. The reduction in duration of immobility in Group V and VI was significant and highly significant respectively as compared to Group III. The augmentation of caffeine with reboxetine is beneficial in treating immobility induced by despair swim test and tail suspension test. The increased concentration of caffeine was proportional to the further decrease in duration of immobility demonstrating an increase in augmentation effect of caffeine with reboxetine. However, further in-detail studies are needed to warrant these outcomes.