Up-regulation of dopamine D(2)L mRNA levels in the ventral tegmental area and dorsal striatum of amphetamine-sensitized C57BL/6 mice: role of Ca(v)1.3 L-type Ca(2+) channels.
Dopamine D(2) long (D(2)L) and D(2) short (D(2)S) 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 D(2)L 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 D(2)S mRNA in the VTA. We further examined the role of the Ca(v)1.3 subtype of L-type Ca(2+) channels in up-regulation of D(2)L and D(2)S 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 D(2)L and D(2)S 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 D(2)S mRNA, but not D(2)L mRNA. In conclusion, our results find that amphetamine increases D(2)L mRNA expression in the dStr and the VTA, an adaptation that correlates with expression of sensitized behavior and dependence on Ca(v)1.3 Ca(2+) channels.
Giordano
T P
TP
Laboratory of Molecular and Developmental Neuroscience, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts, USA.
Satpute
S S
SS
Striessnig
J
J
Kosofsky
B E
BE
Rajadhyaksha
A M
AM
D000661:Amphetamine / Q000494:pharmacology*; D019969:Amphetamine-Related Disorders / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D000818:Animals; D020746:Calcium Channels, L-Type / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D004195:Disease Models, Animal; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009043:Motor Activity / Q000187:drug effects / Q000235:genetics; D017072:Neostriatum / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000235:genetics*; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics; D017557:Ventral Tegmental Area / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology
C485995:Cacna1d protein, mouse; D020746:Calcium Channels, L-Type; D000697:Central Nervous System Stimulants; D012333:RNA, Messenger; D017448:Receptors, Dopamine D2; C113776:dopamine D2L receptor; D000661:Amphetamine