Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10838657 | Pharmacology Biochemistry and Behavior | 2005 | 9 Pages |
Abstract
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 μg, p<0.05; 2.0 μg, 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 μg/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 allopregnanolone (intra-NAcc; 0.5 μg/side) plus fluoxetine (i.p.) or allopregnanolone (s.c.) and the effects of allopregnanolone (intra-NAcc; 1.5 μg/side). Bicuculline (2.0 mg/kg; i.p.) attenuated the synergism between the combination allopregnanolone (intra-NAcc; 0.5 μg/side) plus muscimol (i.p.), but not the synergism of the combination allopregnanolone (intra-NAcc; 0.5 μg/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.
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Authors
M. Molina-Hernández, N.P. Tellez-Alcántara, J. Pérez GarcÃa, J.I. Olivera Lopez, M. Teresa Jaramillo,