Long-term administration with levonorgestrel decreases allopregnanolone levels and alters GABA_A receptor subunit expression and anxiety-like behavior

详细信息    查看全文

• 作者：Patrizia Porcu ; Maria Cristina Mostallino ; Cristiana Sogliano ; Francesca Santoru ; Roberta Berretti ; Aless ; ra Concas
• 关键词：GABAA ; ¦Ã-amino-butyric acid type A ; EE ; Ethinyl Estradiol ; LNG ; Levonorgestrel ; HPG ; hypothalamic&ndash ; pituitary&ndash ; gonadal ; GnRH ; gonadotropin releasing hormone ; LH ; luteinizing hormone ; FSH ; follicle stimulating hormone
• 刊名：Pharmacology Biochemistry and Behavior
• 出版年：2012
• 出版时间：August, 2012
• 年：2012
• 卷：102
• 期：2
• 页码：366-372
• 全文大小：408 K

文摘

Fluctuations in the concentrations of the neuroactive steroid allopregnanolone are thought to influence ¦Ã-amino-butyric acid type A (GABA_A) receptor gene expression and function. Long-term treatment with ethinyl estradiol (EE) plus levonorgestrel (LNG), two of the most widely used steroids in the hormonal contraceptive pill, decreases allopregnanolone levels in rat cerebral cortex and plasma, alters GABA_A receptor expression and induces anxiety-like behavior. We evaluated which component of the hormonal contraceptive pill is responsible for the aforementioned changes. Female rats were injected subcutaneously (s.c.) with EE (0.030 mg) or LNG (0.125 mg) once a day for 4 weeks. Compared to the respective vehicle-treated control groups, EE decreased cerebral cortical levels of allopregnanolone, progesterone and pregnenolone by 76, 72 and 33 % , respectively and hippocampal levels by 52, 56 and 50 % , respectively. Likewise, LNG decreased cerebral cortical levels of allopregnanolone, progesterone and pregnenolone by 75, 68 and 33 % , respectively, and hippocampal levels by 55, 65 and 60 % , respectively. Administration of LNG, but not EE, increased the abundance of the ¦Ã2 subunit peptide in cerebral cortex and hippocampus by 38 and 59 % , respectively. Further, LNG, but not EE, decreased the time spent and the number of entries into the open arms of the elevated plus maze by 56 and 43 % , respectively, an index of anxiety-like behavior. These results suggest that alterations in GABA_A receptor subunit expression and anxiety-like behavior induced by long-term treatment with combined EE/LNG appear to be caused by LNG. Given that both EE and LNG decrease allopregnanolone levels in a similar manner, these results further suggest that changes in allopregnanolone levels are not associated with GABA_A receptor expression.