Effects of cocaine base paste on anxiety-like behavior and immediate-early gene expression in nucleus accumbens and medial prefrontal cortex of female mice

BRUNO G. BERARDINO; ESTEFANÍA A. FESSER; LAURA BELLUSCIO; GIANATIEMPO, OCTAVIO; NICOLÁS PREGI; EDUARDO T. CÁNEPA

PSYCHOPHARMACOLOGY

SPRINGER

Lugar: Berlin; Año: 2019

0033-3158

Rationale: Cocaine base paste (CBP) is an illegal drug of abuse usually consumed byadolescents in a socio-economically vulnerable situation. Repeated drug use targetskey brain circuits disrupting the processes that underlie emotions and cognition. At thebasis of such neuroadaptations lie changes in the expression of immediate-early genes(IEGs). Nevertheless, changes in transcriptional regulation associated with CBPconsumption remain unknown.Objectives: We aimed to describe behavioral phenotype related to locomotion, anxietylikebehavior and memory of CBP-injected mice and to study IEGs expression after anabstinence period.Methods: Five-week old female CF-1 mice were i.p. injected daily with vehicle or CBP(40 mg/kg) for 10 days and subjected to a 10-day period of abstinence. Open field andnovel object recognition tests were used to evaluate locomotion and anxiety-likebehaviors and recognition memory, respectively, during chronic administration andafter abstinence. After abstinence prefrontal cortex (mPFC) and nucleus accumbens(NAc) were isolated and gene expression analysis performed through real-time PCR.Results: We found an increase in locomotion and anxiety-like behavior during CBPadministration and after the abstinence period. Furthermore, the CBP group showedimpaired recognition memory after abstinence. Egr1, FosB, ΔFosB, Arc, Bdnf and TrkBexpression was upregulated in CBP-injected mice in NAc and FosB, ΔFosB, Arc andNpas4 expression was downregulated in mPFC. We generated an anxiety score andfound positive and negative correlations with IEGs expression in NAc and mPFC,respectively.Conclusion: Our results suggest that chronic CBP exposure induced alterations inanxiety-like behavior and recognition memory. These changes were accompanied byaltered IEGs expression.