EXPRESSION OF DOPAMINE TRANSPORTER AND VESICULAR MONOAMINE TRANSPORTER-2 MESSENGER-RNAS IN RAT MIDBRAIN AFTER REPEATED AMPHETAMINE ADMINISTRATION

The dopamine transporter (DAT) in pre-synaptic membranes and the vesic ular monoamine transporter 2 (VMAT2) in membranes of synaptic vesicles are involved in mediating the acute effects of amphetamine on dopamin e transmission. Therefore, using a quantitative method of in situ hybr idization and computerized image analysis, the expression of DAT and V MAT2 mRNAs was examined in rats treated for 5 days with amphetamine an d killed 3 or 14 days after the last injection. We examined ventral te gmental area (VTA), substantia nigra (SN) and the transitional zone be tween VTA and SN. Each of these regions was further subdivided into ro stral, intermediate and caudal portions. In control rats, autoradiogra phs revealed a gradient of both DAT and VMAT2 mRNA levels, decreasing gradually from rostral to caudal rat midbrain. After 3 days of withdra wal, a significant increase in DAT mRNA levels was found in rostral po rtions of VTA (117.9 + 5.8% of control group), SN (116.5 + 4.54%) and the transitional zone (119.6 + 5.6%) and in the intermediate portion o f SN (113.5 + 4.3%). VMAT2 mRNA was significantly increased only in ro stral 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 towa rds increased DAT mRNA levels in intermediate-caudal portions of midbr ain, 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 mo dest and regionally selective effects on DAT and VMAT2 mRNA expression in subpopulations of midbrain dopamine neurons. (C) 1997 Elsevier Sci ence B.V.