Expression of dopamine transporter and vesicular monoamine transporter 2 mRNAs in rat midbrain after repeated amphetamine administration

Abstract

The dopamine transporter (DAT) in pre-synaptic membranes and the vesicular monoamine transporter 2 (VMAT2) in membranes of synaptic vesicles are involved in mediating the acute effects of amphetamine on dopamine transmission. Therefore, using a quantitative method of in situ hybridization and computerized image analysis, the expression of DAT and VMAT2 mRNAs was examined in rats treated for 5 days with amphetamine and killed 3 or 14 days after the last injection. We examined ventral tegmental area (VTA), substantia nigra (SN) and the transitional zone between VTA and SN. Each of these regions was further subdivided into rostral, intermediate and caudal portions. In control rats, autoradiographs revealed a gradient of both DAT and VMAT2 mRNA levels, decreasing gradually from rostral to caudal rat midbrain. After 3 days of withdrawal, a significant increase in DAT mRNA levels was found in rostral portions of VTA (117.9+5.8% of control group), SN (116.5+4.5%) and the transitional zone (119.6+5.6%) and in the intermediate portion of SN (113.5+4.3%). VMAT2 mRNA was significantly increased only in rostral and intermediate portions of the transitional zone (120.9+4.8 and 113.6+4.1%). After 14 days of withdrawal, there was a trend towards increased DAT mRNA levels in intermediate-caudal portions of midbrain, but a statistically significant increase was observed only in the intermediate portion of VTA (120.2+7.9%). No changes in VMAT2 mRNA levels were found. Thus, repeated amphetamine administration exerts modest and regionally selective effects on DAT and VMAT2 mRNA expression in subpopulations of midbrain dopamine neurons.