Up-regulation of dopamine D2L mRNA levels in the ventral tegmental area and dorsal striatum of amphetamine-sensitized C57BL/6 mice:: role of Cav1.3 L-type Ca2+ channels

Dopamine D-2 long (D2L) and D-2 short (D2S) isoforms of the D-2 receptor play an important role in psychostimulant-induced neuronal adaptations. In this study, we used quantitative real-time PCR to specifically amplify these two splice variants to examine their mRNA expression in the dorsal striatum (dStr), nucleus accumbens (NAc) and the ventral tegmental area (VTA) of amphetamine-sensitized C57BL/6 mice. We found a significant increase in D2L mRNA in the VTA and dStr of amphetamine-treated mice that positively correlated with the sensitized locomotor response. We also found a significant increase in D2S mRNA in the VTA. We further examined the role of the Ca(v)1.3 subtype of L-type Ca2+ channels in up-regulation of D2L and D2S mRNA in the VTA. Amphetamine-pretreated Ca(v)1.3 wild-type (Ca(v)1.3(+/+)) mice exhibited sensitized behavior and a significant increase in D2L and D2S mRNA compared with saline-pretreated mice Amphetamine-pretreated homozygous Ca(v)1.3 knockout (Ca(v)1.3(-/-)) mice did not exhibit sensitized behavior. There was a significant increase in D2S mRNA, but not D2L mRNA. In conclusion, our results find that amphetamine increases D2L mRNA expression in the dStr and the VTA, an adaptation that correlates with expression of sensitized behavior and dependence on Ca(v)1.3 Ca2+ channels.