Activation of G-protein coupled estradiol receptor 1 in the dorsolateral striatum attenuates preference for cocaine and saccharin in male but not female rats

Ja, Quigley; Becker, J. Ernestine

doi:10.1101/824078

Cited by 1 publication

(1 citation statement)

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“…We also identified upstream regulators that may have sex-specific roles in the VTA. For example, pharmacological studies suggest that ER-alpha activity, one upstream regulator we identified from both HC Chronic and IVSA samples, is protective against the effects of cocaine in males, but promotes cocaine action in females [69]. Examining the putative downstream targets of ERalpha that we identified in our datasets within both males and females may provide new insight into the sex-dependent roles of ER-alpha in response to cocaine.…”

Section: Discussionmentioning

confidence: 86%

Cocaine induces paradigm-specific changes to the transcriptome within the ventral tegmental area

Campbell

Chen

Beardwood

et al. 2021

Neuropsychopharmacol.

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During the initial stages of drug use, cocaine-induced neuroadaptations within the ventral tegmental area (VTA) are critical for drug-associated cue learning and drug reinforcement processes. These neuroadaptations occur, in part, from alterations to the transcriptome. Although cocaine-induced transcriptional mechanisms within the VTA have been examined, various regimens and paradigms have been employed to examine candidate target genes. In order to identify key genes and biological processes regulating cocaine-induced processes, we employed genome-wide RNA-sequencing to analyze transcriptional profiles within the VTA from male mice that underwent one of four commonly used paradigms: acute home cage injections of cocaine, chronic home cage injections of cocaine, cocaine-conditioning, or intravenous-self administration of cocaine. We found that cocaine alters distinct sets of VTA genes within each exposure paradigm. Using behavioral measures from cocaine self-administering mice, we also found several genes whose expression patterns corelate with cocaine intake. In addition to overall gene expression levels, we identified several predicted upstream regulators of cocaine-induced transcription shared across all paradigms. Although distinct gene sets were altered across cocaine exposure paradigms, we found, from Gene Ontology (GO) term analysis, that biological processes important for energy regulation and synaptic plasticity were affected across all cocaine paradigms. Coexpression analysis also identified gene networks that are altered by cocaine. These data indicate that cocaine alters networks enriched with glial cell markers of the VTA that are involved in gene regulation and synaptic processes. Our analyses demonstrate that transcriptional changes within the VTA depend on the route, dose and context of cocaine exposure, and highlight several biological processes affected by cocaine. Overall, these findings provide a unique resource of gene expression data for future studies examining novel cocaine gene targets that regulate drug-associated behaviors.

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Section: Discussionmentioning

confidence: 86%