Changes in the glutamate biomarker expression in rats vulnerable or resistant to the rewarding effects of cocaine and their reversal by ceftriaxone

摘要

Literature data show diverse vulnerability to the rewarding effects of cocaine in human as well as in laboratory animals. The molecular mechanisms of these differences have not been discovered yet. While the initial effects of cocaine depend primarily on the dopamine system, numerous studies have shown that adaptation within the glutamatergic system is responsible for the development of addiction. In this paper, we used the unbiased conditioned place preference (CPP) to identify rats showing a vulnerable or resistant phenotype to the rewarding effects of cocaine. Next, we investigated the expression of membrane glutamate transporter proteins: GLT-1 and xCT in selected brain structures in the above-mentioned groups of rats. Moreover, we determined the nuclear level of NF-kappa B and Nrf2 to verify whether changes in GLT-1 and xCT expression correlate with NF-kappa B and Nrf2 levels, respectively. In addition, we determined GLT-1, NF-kappa B, xCT and Nrf2 mRNA levels to verify the involvement of transcriptional mechanisms. We also analyzed the ability of the beta-lactam antibiotic, ceftriaxone, to attenuate the persistence of CPP after a cocaine-free period in animals showing vulnerability to cocaine rewarding effects, and furthermore we determined GLT-1, xCT, NF-kappa B and Nrf2 protein expression. Our findings demonstrated molecular and neurochemical differences in the response to cocaine administration that are characteristic of the phenotype vulnerable or resistant to the rewarding effects of cocaine.