Iptkalim inhibits cocaine challenge-induced enhancement of dopamine levels in nucleus accumbens and striatum of rats by up-regulating Kir6.1 and Kir6.2 mRNA expression.
OBJECTIVE
To investigate the effect and mechanism of novel ATP-sensitive potassium channel opener (KCO) iptkalim (IPT) on acute and cocaine challenge-induced alterations in the levels of dopamine (DA) and glutamate (Glu) from nucleus accumbens (NAc), striatum, and prefrontal cortex (PFC) in rats.


METHODS
The levels of DA and Glu were assayed using high performance liquid chromatography (HPLC) combined with amperometric and fluorescent detection, respectively. The mRNA levels of Kir6.1, Kir6.2, SUR1, and SUR2 were measured by semiquantitative reverse transcription polymerase chain reaction (RT-PCR).


RESULTS
IPT did not affect acute cocaine (30 mg/kg, ip)-induced elevations in either DA levels from NAc and striatum or Glu levels from NAc and PFC. An acute cocaine challenge (30 mg/kg, ip) on d 21 after withdrawal caused an elevation in DA levels in NAc and striatum. Moreover, the same treatment also increased Glu levels in PFC and NAc of cocaine-pretreated rats. Repeated IPT injections reversed cocaine challenge-induced DA increase in NAc and striatum. Cocaine challenge increased Kir6.1 and Kir6.2 mRNA expression in striatum and NAc and only elevate Kir6.2 expression in PFC in both cocaine-pretreated rats and rats pretreated with IPT plus cocaine. Moreover, expression of Kir6.1 and Kir6.2 mRNA was augmented in rats pretreated with IPT plus cocaine compared to rats pretreated with cocaine alone. No significant change was found in the SUR1 and SUR2 expression of all four groups.


CONCLUSIONS
IPT inhibited cocaine challenge-induced enhancement of DA levels in NAc and striatum by up-regulating Kir6.1 and Kir6.2 mRNA expression.
Liu
Yun
Y
Department of Pharmacology and Neurobiology, Nanjing Medical University, Nanjing 210029, China. ghu@njmu.edu.cn
He
Hai-Rong
HR
Ding
Jian-Hua
JH
Gu
Bing
B
Wang
Hai
H
Hu
Gang
G
D000818:Animals; D003042:Cocaine / Q000037:antagonists & inhibitors*; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D018698:Glutamic Acid / Q000378:metabolism; D008297:Male; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000378:metabolism; D024661:Potassium Channels, Inwardly Rectifying / Q000235:genetics / Q000378:metabolism*; D017397:Prefrontal Cortex / Q000378:metabolism; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015854:Up-Regulation
D024661:Potassium Channels, Inwardly Rectifying; D012333:RNA, Messenger; D018698:Glutamic Acid; D003042:Cocaine; D004298:Dopamine