Δ(9)-Tetrahydrocannabinol Experience Influences ΔFosB and Downstream Gene Expression in Prefrontal Cortex

Cannabis and Cannabinoid Research
Matthew F LazenkaLaura J Sim-Selley

Abstract

Introduction: Repeated administration of abused drugs, including Δ(9)-tetrahydrocannabinol (THC), induces the stable transcription factor ΔFosB in dopaminergic terminal field regions of the mesolimbic system. These studies investigated the effect of prior repeated THC treatment on THC-induced ΔFosB expression and regulation of downstream targets in the forebrain. Methods: Mice received THC (10 mg/kg) or vehicle twice daily for 13 days, and then half of each group received a single injection of THC or vehicle 45 min before brain collection. ΔFosB messenger RNA (mRNA) and protein were measured by polymerase chain reaction and immunoblotting, respectively. Potential downstream targets of ΔFosB induction were measured by immunoblot. Results: THC injection in mice with a history of repeated THC treatment enhanced ΔFosB expression as compared with vehicle in the prefrontal cortex (PFC), nucleus accumbens (NAc), and amygdala. This change occurred concomitantly with an increase in ΔFosB mRNA in the PFC and NAc. THC injection in mice with a history of repeated THC treatment increased expression of cyclin-dependent kinase 5 (Cdk5) and its regulatory protein p35 only in the PFC. This increase in Cdk5 and p35 expression in PFC was also fou...Continue Reading

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BETA
transgenic
electrophoresis

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Prism
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