Allopregnanolone microinjected into the lateral septum or dorsal hippocampus reduces immobility in the forced swim test: participation of the GABAA receptor

Allopregnanolone is a 5 alpha-reduced metabolite of progesterone with actions on gamma-aminobutyric acid-A (GABA(A)) receptors that produce antidepressant-like effects. However, little is known about the target brain regions that mediate its antidepressant-like effects. In this study, allopregnanolone (2.01 mu g/0.3 mu l/rat) or its vehicle (35% cyclodextrin solution) were microinjected into the lateral septum, septofimbrial, or dorsal hippocampus of male Wistar rats that had previously received intraperitoneal injections of either saline or the GABA(A) antagonist bicuculline (1.0 mg/kg), and its effects were evaluated in the open field and forced swim tests. Allopregnanolone microinjected into the lateral septum or dorsal hippocampus, but not septofimbrial nucleus, induced a longer latency to the first immobility and a shorter total immobility time in the forced swim test compared with vehicle. Bicuculline pretreatment reversed the effect of allopregnanolone. None of the treatments produced significant changes in crossings in the open field test. In conclusion, allopregnanolone produces an antidepressant-like effect in rats submitted to the forced swim test through actions on GABA(A) receptors located in the lateral septum and dorsal hippocampus, which is consistent with the antistress effect of GABA(A) agonists in these particular brain structures. Behavioural Pharmacology 20:614-622 (c) 2009 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.