Antidepressant-like actions of intra-accumbens infusions of allopregnanolone in ovariectomized Wistar rats

This study was aimed to verify the role of the nucleus accumbens (NAcc) in the antidepressant-like effects of allopregnanolone in ovariectomized rats forced to swim. The interaction between infusions of allopregnanolone (intra-NAcc) with systemic administrations of allopregnanolone, muscimol, fluoxetine and GABA-A antagonists was assessed. Results showed that allopregnanolone (intra-NAcc; 1.5 mu g, p < 0.05; 2.0 mu g, p < 0.05) or systemic injections of allopregnanolone (1.5 mg/kg, p < 0.05; 2.0 mg/kg, p < 0.05; s.c.) or muscimol (0.3 mg/kg, p < 0.05; 0.6 mg/kg,p < 0.05; i.p.) reduced immobility by increasing climbing in the forced swimming task (FST), whereas fluoxetine (1.0 mg/ kg, p < 0.05; 2.0 mg/kg, p < 0.05; i.p.) reduced immobility by increasing swimming. Allopregnanolone (intra-NAcc; 0.5 mu g/side) synergized with systemic doses of allopregnanolone (0.5 mg/kg; p < 0.05), muscimol (0.1 mg/kg; p < 0.05) or fluoxetine (0.5 mg/kg; p < 0.05) and reduced immobility by increasing climbing. Picrotoxin (0.125 mg/kg; i.p.) attenuated the synergism of the combination allopregnanollone (intra-NAcc; 0.5 mu g/side) plus fluoxetine (i.p.) or allopregnanolone (s.c.) and the effects of allopregnanolone (intra-NAcc; 1.5 mu g/side). Bicuculline (2.0 mg/kg; i.p.) attenuated the synergism between the combination allopregnanolone (intra-NAcc; 0.5 mu g/side) plus muscimol (i.p.), but not the synergism of the combination allopregnanolone (intra-NAcc; 0.5 mu g/side) plus allopregnanolone (s.c.). In conclusion, allopregnanolone (systemic injections or intra-NAcc), fluoxetine or muscimol produced antidepressant-like effects in the FST. Subthreshold doses of allopregnanolone (intra-NAcc) synergized with systemic subthreshold doses of fluoxetine, muscimol or allopregnanolone. Antagonists of the GABA-A receptor canceled the synergism. (c) 2004 Elsevier Inc. All rights reserved.