GSE185195 Gene expression profiling of the nucleus accumbens and dorsolateral striatum in a two-hit model combining maternal immune activation and peripubertal stress in rats

Contributors : Roberto Capell án ; Alejandro Higuera-MatasSeries Type : Expression profiling by high throughput sequencingOrganism : Rattus norvegicusSubstance use disorders are more prevalent in schizophrenia, worsening its course and prognosis. Here, we used a double-hit rat model, combining maternal immune activation (MIA) and peripubertal stress (PUS), to study cocaine addiction and the underlying neurobehavioral alterations. We injected lipopolysaccharide (LPS) or saline on gestational days 15 and 16 to pregnant rats. Their male offspring were then subjected to unpredictable stress during adolescence. When rats reached adulthood, we studied their cocaine addiction-like behavior, impulsivity and conditioning processes, and several aspects of brain structure and function by MRI, PET and RNAseq. MIA facilitated the acquisition of cocaine self-administration but PUS reduced cocaine intake, an effect that was reversed by MIA. MIA increased motivation for cocaine and revearsed the effects of PUS during extended access. Incubation of seeking was unaffected. Neither hit alone nor their combination impacted pavlovian or instrumental learning or impulsiveness. At the brain level, PUS reduced hippocampal volume and hyperactivated the dorsal subiculum. When combined, both hits altered the structure and function of the dorsal striatum increasing its volume and interferring with glutamatergic dynamics. MIA alone had no effect on the gene expression of the nucleus accumbens but, whe...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Rattus norvegicus Source Type: research