Title | 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. |
Publication Type | Journal Article |
Year of Publication | 2006 |
Authors | Giordano TP, Satpute SS, Striessnig J, Kosofsky BE, Rajadhyaksha AM |
Journal | J Neurochem |
Volume | 99 |
Issue | 4 |
Pagination | 1197-206 |
Date Published | 2006 Nov |
ISSN | 0022-3042 |
Keywords | Amphetamine, Amphetamine-Related Disorders, Animals, Calcium Channels, L-Type, Central Nervous System Stimulants, Disease Models, Animal, Male, Mice, Mice, Inbred C57BL, Mice, Knockout, Motor Activity, Neostriatum, Receptors, Dopamine D2, RNA, Messenger, Up-Regulation, Ventral Tegmental Area |
Abstract | 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. |
DOI | 10.1111/j.1471-4159.2006.04186.x |
Alternate Journal | J. Neurochem. |
PubMed ID | 17026527 |
Grant List | P 17159 / / Austrian Science Fund FWF / Austria K01DA14057 / DA / NIDA NIH HHS / United States P30NS45776 / NS / NINDS NIH HHS / United States K02DA00354 / DA / NIDA NIH HHS / United States 1S10RR022370-01 / RR / NCRR NIH HHS / United States |