Differential effects of anesthetics on cocaine's pharmacokinetic and pharmacodynamic effects in brain.
Differential effects of anesthetics on cocaine's pharmacokinetic and pharmacodynamic effects in brain.
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麻醉药对可卡因的药代动力学和药效动力学作用的差异作用。
DOI：
10.1111/j.1460-9568.2009.06931.x
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发表时间：
2009-10
期刊：
影响因子：
--
通讯作者：
Benveniste H
中科院分区：
文献类型：
--
作者：
Du C;Tully M;Volkow ND;Schiffer WK;Yu M;Luo Z;Koretsky AP;Benveniste H
Most studies of cocaine’s effects on brain activity in laboratory animals are preformed under anesthesia, which could potentially affect the physiological responses to cocaine. Here we assessed the effects of two commonly used anesthetics (α-chloralose and isofluorane) on the effects of acute cocaine (1 mg/kg iv) on cerebral-blood-flow (CBF), cerebral-blood-volume (CBV), and tissue-hemoglobin-oxygenation (StO2) using optical techniques and cocaine’s pharmacokinetics and binding in the rat brain using PET and [11C]cocaine. We showed that acute cocaine at a dose abused by cocaine abusers decreased CBF, CBV and StO2 in rats anesthetized with isoflurane, whereas it increased these parameters in rats anesthetized with α-chloralose. Importantly, in isoflurane-anesthetized animals cocaine-induced changes in CBF and StO2 were coupled whereas for α-chloralose these measures were uncoupled. Moreover, the clearance of [11]cocaine from brain was faster for isoflurance (peak-half-clearance 15.8±2.8 min) than for α-chloralose (27.5±0.6 min) and the ratio of the specific to non-specific binding of [11C]cocaine in brain was higher for isoflurane (3.37 ± 0.32) than for α-chloralose anesthetized rats (2.24 ± 0.4). For both anesthetics cocaine induced changes in CBF followed the fast uptake of [11C]cocaine in brain (peaking at ~ 2.5–4 minutes) but only for isoflurane did the duration of the CBV and StO2 changes correspond to the rate of [11C]cocaine’s clearance from the brain. These results demonstrate that anesthetics influence cocaine’s hemodynamic and metabolic changes in brain and its binding and pharmacokinetics, which highlights the need to better understand the interactions between anesthetics and pharmacological challenges in brain functional imaging studies.
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影响因子：
2.5
作者：
Gozzi, Alessandro;Ceolin, Laura;Bifone, Angelo
通讯作者：
Bifone, Angelo
影响因子：
--
作者：
BARNETT, NJ;DOUGHERTY, G;PETTINGER, SJ
通讯作者：
PETTINGER, SJ
影响因子：
3.4
作者：
FARDE, L;PAULI, S;STONEELANDER, S
通讯作者：
STONEELANDER, S
影响因子：
5.7
作者：
Dunn, AK;Devor, A;Boas, DA
通讯作者：
Boas, DA
影响因子：
5.7
作者：
Jones, M;Berwick, J;Mayhew, J
通讯作者：
Mayhew, J