Estrogen regulates responses of dopamine neurons in the ventral tegmental area to cocaine

doi:10.1007/s00213-008-1188-6

CORC > 上海药物研究所 > 中国科学院上海药物研究所 > 药理学第二研究室

	Estrogen regulates responses of dopamine neurons in the ventral tegmental area to cocaine
	Zhang, Die; Yang, Shen; Yang, Chunhao; Jin, Guozhang; Zhen, Xuechu
刊名	PSYCHOPHARMACOLOGY
	2008-09
卷号	199 期号:4 页码:625-635
关键词	cocaine dopaminergic neurons firing ventral tegmental area slow oscillation estrogen
ISSN号	0033-3158
DOI	10.1007/s00213-008-1188-6
文献子类	Article
英文摘要	Rationale Sex differences in cocaine abuse have been well documented. However, the underlying mechanism remains unclear. Objectives To explore the potential role of ovarian hormones in the regulation of dopamine (DA) neuron firing activity in ventral tegmental area (VTA) induced by acute cocaine in intact female or ovariectomized (OVX) rats. Results The basal firing activity of VTA DA neurons was changed in a manner phase-locked to the estrous cycle: being highest in estrus and lowest in proestrus. Acute cocaine produced greater inhibition (P < 0.05) on the firing of VTA DA neurons during proestrus than during estrus. The inhibitory effect was completely blocked by OVX and restored by replacement of 17-beta-estradiol or, to a less extent, by replacement of progesterone. In addition, we also detected female hormone-associated changes in slow oscillation in VTA DA neurons. The results indicate that ovarian hormones, particularly estrogen, not only synergize with the inhibitory effect of cocaine on VTA DA neuron activity but also play an essential role in maintaining the sensitivity of DA neurons to cocaine-mediated inhibition on firing. Moreover, pretreatment of estrogen receptor (ER) antagonist raloxifene or a selective ER alpha antagonist Y134 largely attenuated the cocaine-inhibited DA neuron firing. We also found that cocaine-induced locomotor activity was estrous cycle dependant; 17-beta-estradiol but not progesterone replacement restored the cocaine-induced locomotor activity in OVX rats. Conclusion The present results demonstrated that ovarian hormones, particularly estrogen, produce profound effect on VTA DA neuron activity, which, in turn, may contribute to the sex differences in response to psychostimulants.
WOS关键词	CENTRAL-NERVOUS-SYSTEM ; SEX-DIFFERENCES ; STRIATAL DOPAMINE ; FEMALE RATS ; DRUG-ABUSE ; EXTRACELLULAR ELECTROPHYSIOLOGY ; OVARIECTOMIZED RATS ; NUCLEUS-ACCUMBENS ; BEHAVIORAL SENSITIZATION ; PREFRONTAL CORTEX
WOS研究方向	Neurosciences & Neurology ; Pharmacology & Pharmacy ; Psychiatry
语种	英语
出版者	SPRINGER
WOS记录号	WOS:000257957400012
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/272830]
专题	药理学第二研究室中科院受体结构与功能重点实验室新药研究国家重点实验室
通讯作者	Zhen, Xuechu
作者单位	Chinese Acad Sci, State Key Lab Drug Res, Dept Neuropharmacol, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China
推荐引用方式 GB/T 7714	Zhang, Die,Yang, Shen,Yang, Chunhao,et al. Estrogen regulates responses of dopamine neurons in the ventral tegmental area to cocaine[J]. PSYCHOPHARMACOLOGY,2008,199(4):625-635.
APA	Zhang, Die,Yang, Shen,Yang, Chunhao,Jin, Guozhang,&Zhen, Xuechu.(2008).Estrogen regulates responses of dopamine neurons in the ventral tegmental area to cocaine.PSYCHOPHARMACOLOGY,199(4),625-635.
MLA	Zhang, Die,et al."Estrogen regulates responses of dopamine neurons in the ventral tegmental area to cocaine".PSYCHOPHARMACOLOGY 199.4(2008):625-635.