Elevated BDNF mRNA expression in the medial prefrontal cortex after d-amphetamine reinstated conditioned place preference in rats

Abstract

Drug addiction behavior that is established and maintained by psychostimulants has been shown to be associated with the expression of brain-derived neurotrophic factor (BDNF) in the mesolimbic dopamine (DA) system. Cocaine has been used for most prior studies testing this effect of psychostimulants and therefore relatively little is known about its counterpart amphetamine (AMP). To fill this gap, the present study was designed to test whether BDNF mRNA expression levels in the DA terminal regions were changed specifically by d-AMP-induced conditioned place preference (CPP) followed by drug-primed reinstatement. The dose of d-AMP, 1mg/kg, was confirmed to significantly induce CPP. Using this dose, a group of rats was initially subjected to d-AMP CPP, which was followed by entry into an extinction protocol with an additional 3-day withdrawal before a drug-primed reinstatement test was carried out. Following extinction of d-AMP CPP, a lower dose of d-AMP, namely 0.75mg/kg, was able to significantly reinstate CPP. The BDNF mRNA levels in the selected brain areas were determined by real-time polymerase chain reaction (PCR) after the CPP and reinstatement. The BDNF mRNA level in the medial prefrontal cortex (mPFC) was significantly increased after the reinstatement, but not the CPP test. And, none of the other four assessed brain areas showed any change in BDNF mRNA level after d-AMP CPP or reinstatement. These findings support the notion that BDNF is involved in drug-seeking behavior and indicate that d-AMP reinstatement after extinction may be linked to an increase in BDNF mRNA expression in the mPFC.

Keywords: addiction; brain-derived neurotrophic factor; drug seeking; mesocorticolimbic dopamine; place conditioning.