Gabapentin, an anticonvulsant drug, used for neuropathic pain, also it has protective effects against psychological stress with a mild side-effect profile. Evidence link high glucocorticoids blood levels and stress to nitric oxide and depression. Thus the aim was to assess the effectiveness of gabapentin in treating depression following dexamethasone (Dex) administration, exposure to stress, and complete Freund's adjuvant (CFA) induced inflammation in mice.

Male NMRI mice (weighing 28 ± 2 g) were used. Dex (15 μg/kg, subcutaneously) was administered for 7 days, stress was induced by water avoidance stress (WAS), and CFA was injected into the mouse's paw for 17 days. Gabapentin or imipramine (both 10 mg/kg, intraperitonealy) were administered for 7 days. Locomotor activity, the force swim test (FST), sucrose preference (SP) test, and the novelty suppressed feeding (NSFT) were measured.

During the FST, immobility time significantly increased by Dex, WAS and CFA compared to the control group. WAS and CFA groups increased latency time and reduced food consumption in NSFT, SP also decrease. Treatment with gabapentin (alike imipramine) along with Dex, stress, or CFA significantly reduced immobility time in FST, and SP increased. During NSFT in stress and CFA groups treated with gabapentin latency time reduced and food consumption increased. There was no significant alteration in the animals' locomotor activity.

In conclusion, gabapentin prevented dexamethasone, stress or inflammation-induced depression in mice. Thus it is promising for depression related to these conditions in patients.