1.Mediating effect of dopamine D3 receptors on Jak2 and GABAAalpha1 expression in mouse brains induced by cocaine.
Nu-yun LIU ; Lu ZHANG ; Lin ZHANG ; Xiao-ning WANG
Chinese Medical Journal 2007;120(10):910-914
BACKGROUNDCocaine addiction may involve complex neuroadaptations, including many changes of genes expression. Dopamine D3 receptors play an important role in cocaine addiction; however, its role in cocaine induced gene expression change is poorly understood. To identify the changes in gene expression induced by repeated cocaine exposure through D3 dopamine receptors, we compared the expression of four molecules: Janus kinase 2 (Jak2), g-aminobutanoic acid receptor subunit alpha 1 (GABAAalpha1), glutamate receptor AMPA3 alpha 3 (GluR 3) and stromal cell derived factor 1 (SDF1). These four have been implicated in mediating the actions of cocaine in the nucleus accumbens (NAc) and caudoputamen (CPu) in mice after acute and repeated cocaine exposure.
METHODSFor the acute and repeated injections, the mice were divided into four groups: 30 mg/kg cocaine, nafadotride 0.5 mg/kg + cocaine 30 mg/kg, nafadotride 0.5 mg/kg, and saline as the basal group. The expression of Jak2, GABAAalpha1, GluR 3 and SDF1 were assayed by Western blot, quantitative real-time RT-PCR and immunohistochemistry.
RESULTSTwenty-four hours after seven consecutive days of repeated cocaine exposure, the expression of GABAAalpha1 decreased in cocaine group compared with basal line and further decreased in the cocaine + nafadotride group and remained at basal level in the nafadotride group. Similarly, the Jak2 expression decreased in cocaine group compared with base line. However, the levels of Jak2 increased in cocaine + nafadotride group compared with cocaine group, while remained at basal level in nafadotride group.
CONCLUSIONSGABAAalpha1 and Jak2 may be involved in chronic cocaine induced neuroadaptations. D3 dopamine receptors play an important role in the expression of these genes.
Animals ; Brain ; drug effects ; metabolism ; Cocaine ; pharmacology ; Female ; Gene Expression Regulation ; drug effects ; Immunohistochemistry ; Janus Kinase 2 ; analysis ; genetics ; Male ; Mice ; Receptors, Dopamine D3 ; physiology ; Receptors, GABA-A ; analysis ; genetics ; Reverse Transcriptase Polymerase Chain Reaction
2.Dopamine receptors oppositely regulate cocaine-induced transcription factor CREB activation.
Nu-yun LIU ; Lin ZHANG ; Xiao-ning WANG ; Lu ZHANG
Journal of Southern Medical University 2006;26(6):715-718
OBJECTIVETo study the role of dopamine receptors in the regulation of the activity of transcription factor cAMP response element-binding protein (CREB) after cocaine treatment.
METHODSBy using dopamine receptor antagonists SCH23390 and nafadotride, the activation of CREB by D1 and D3 dopamine receptors after cocaine treatment and role of extracellular signal-regulated kinase (ERK) in cocaine-induced CREB activation were examined by Western blotting, which was also employed for determination of the effect of SCH23390 and nafadotride on CREB activation.
RESULTSD1 receptor antagonist could inhibit cocaine-induced CREB activation, while D3 receptor antagonist enhanced cocaine-induced CREB activation. Dopamine receptor antagonists SCH23390 and nafadotride did not induce CREB activation. SL327, a MEK inhibitor, inhibited cocaine-induced CREB activation.
CONCLUSIOND1 and D3 dopamine receptors can oppositely regulate CREB activation after cocaine treatment and this regulation depends on ERK signaling pathway.
Animals ; Benzazepines ; pharmacology ; Blotting, Western ; Cocaine ; pharmacology ; Cyclic AMP Response Element-Binding Protein ; metabolism ; Dopamine Antagonists ; pharmacology ; Dopamine Uptake Inhibitors ; pharmacology ; Extracellular Signal-Regulated MAP Kinases ; metabolism ; Mice ; Naphthalenes ; pharmacology ; Pyrrolidines ; pharmacology ; Receptors, Dopamine D1 ; antagonists & inhibitors ; physiology ; Receptors, Dopamine D3 ; antagonists & inhibitors ; physiology ; Signal Transduction ; drug effects
3. Adolescent stress increases depression-like behaviors and alters the excitatory-inhibitory balance in aged mice
Hong-Li WANG ; Ya-Xin SUN ; Xiao LIU ; Han WANG ; Yu-Nu MA ; Yun-Ai SU ; Ji-Tao LI ; Tian-Mei SI
Chinese Medical Journal 2019;132(14):1689-1699
Background:
Depression affects approximately 5% of elderly people and its etiology might be related to chronic stress exposure during neurodevelopmental periods. In this study, we examined the effects of adolescent chronic social stress in aged mice on depressive behaviors and the excitatory-inhibitory (E/I) balance in stress-sensitive regions of the brain.
Methods:
Sixty-four adolescent, male C57BL/6 mice were randomly assigned to either the 7-week (from post-natal days 29 to 77) social instability stress (stress group,
4.The Nucleus Accumbens CRH-CRHR1 System Mediates Early-Life Stress-Induced Sleep Disturbance and Dendritic Atrophy in the Adult Mouse.
Ting WANG ; Yu-Nu MA ; Chen-Chen ZHANG ; Xiao LIU ; Ya-Xin SUN ; Hong-Li WANG ; Han WANG ; Yu-Heng ZHONG ; Yun-Ai SU ; Ji-Tao LI ; Tian-Mei SI
Neuroscience Bulletin 2023;39(1):41-56
Adverse experiences in early life have long-lasting negative impacts on behavior and the brain in adulthood, one of which is sleep disturbance. As the corticotropin-releasing hormone (CRH)-corticotropin-releasing hormone receptor 1 (CRHR1) system and nucleus accumbens (NAc) play important roles in both stress responses and sleep-wake regulation, in this study we investigated whether the NAc CRH-CRHR1 system mediates early-life stress-induced abnormalities in sleep-wake behavior in adult mice. Using the limited nesting and bedding material paradigm from postnatal days 2 to 9, we found that early-life stress disrupted sleep-wake behaviors during adulthood, including increased wakefulness and decreased non-rapid eye movement (NREM) sleep time during the dark period and increased rapid eye movement (REM) sleep time during the light period. The stress-induced sleep disturbances were accompanied by dendritic atrophy in the NAc and both were largely reversed by daily systemic administration of the CRHR1 antagonist antalarmin during stress exposure. Importantly, Crh overexpression in the NAc reproduced the effects of early-life stress on sleep-wake behavior and NAc morphology, whereas NAc Crhr1 knockdown reversed these effects (including increased wakefulness and reduced NREM sleep in the dark period and NAc dendritic atrophy). Together, our findings demonstrate the negative influence of early-life stress on sleep architecture and the structural plasticity of the NAc, and highlight the critical role of the NAc CRH-CRHR1 system in modulating these negative outcomes evoked by early-life stress.
Animals
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Mice
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Corticotropin-Releasing Hormone/metabolism*
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Nucleus Accumbens/metabolism*
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Receptors, Corticotropin-Releasing Hormone/metabolism*
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Sleep
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Sleep Wake Disorders
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Stress, Psychological/complications*