Role of DARPP-32 pathway in cocaine-induced behavioral sex differences
Item
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Title
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Role of DARPP-32 pathway in cocaine-induced behavioral sex differences
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Identifier
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d_2009_2013:2683bd8aea39:10411
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identifier
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10383
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Creator
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Zhou, Luyi,
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Contributor
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Vanya Quinones-Jenab
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Date
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2009
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Language
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English
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Publisher
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City University of New York.
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Subject
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Neurosciences | Cdk5 | cocaine | DARPP-32 | sex differences
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Abstract
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Accumulating evidence suggests that behavioral responses to cocaine are sexually dimorphic: female rats are more sensitive to cocaine. Female rats exhibit exaggerated and more robust locomotor responses to cocaine than do males. Females also more quickly develop cocaine-induced conditioned place preference (CPP) and behavior sensitization with lower doses, and more readily acquire cocaine self-administration. However, the underling mechanisms for this behavioral sex differences remain unknown. The dopamine- and cAMP-regulated phosphoprotein (DARPP-32) signaling pathway has been shown to mediate intracellular responses to acute and chronic cocaine in male rodents. The purpose of this proposal is to assess the role of DARPP-32 pathways in cocaine-induced behavioral sex differences in male and female rats. We hypothesize that acute and chronic cocaine activates DARPP-32 signaling in a sexual dimorphism way. To test this hypothesis, in the acute cocaine experiment, rats received saline or cocaine (30mg/kg), while in the chronic cocaine experiment, rats received saline, acute cocaine or chronic cocaine (15mg/kg), Protein levels of the DARPP-32 signaling proteins in the nucleus accumbens (NAc) and caudate putamen (CPu) were measured via western blot. Locomotor and stereotyped activities were also measured in the chronic cocaine experiment. In the acute cocaine experiment, female rats had heightened basal levels of DARPP-32 cascade; while male rats exhibited higher induction of the cascade after acute cocaine administration. However, these sex differences were mainly observed in the NAc, not CPu. In the chronic cocaine experiment, female rats developed behavior sensitization and tolerance to cocaine earlier than males. In male rats, the heightened DARPP-32 signaling were mostly found in the NAc when behavior sensitization was observed; while in female rats, increased signaling were mostly found in the CPu when behavior tolerance was observed. In addition, the protein levels of several DARPP-32 signaling proteins, including DeltaFosB, FosB, Cdk5 and p35, correlated with the behavior activities. Taken together, these results suggest that DARPP-32 signaling pathway is altered in a sexual dimorphic way after acute and chronic cocaine treatment, and it may play a critical role for the sex differences at the behavior level.
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Type
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dissertation
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Source
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2009_2013.csv
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degree
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Ph.D.
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Program
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Biology
