EXTRACELLULAR CONCENTRATIONS OF COCAINE AND DOPAMINE ARE ENHANCED DURING CHRONIC COCAINE ADMINISTRATION
EXTRACELLULAR CONCENTRATIONS OF COCAINE AND DOPAMINE ARE ENHANCED DURING CHRONIC COCAINE ADMINISTRATION
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DOI：
10.1111/j.1471-4159.1990.tb04562.x
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发表时间：
1990-09-01
影响因子：
4.7
通讯作者：
JUSTICE, JB
中科院分区：
文献类型：
--
作者：
PETTIT, HO;PAN, HT;JUSTICE, JB
长期服用可卡因会显著增加可卡因诱导的运动活动和刻板印象。采用微透析法对慢性和急性可卡因处理动物的伏隔核细胞外多巴胺(DA)和可卡因浓度(N ACC)及血浆中可卡因浓度进行监测。在可卡因挑战注射后，每天接受可卡因注射10天或30天的动物的可卡因和多巴胺浓度随着时间的推移都显著高于每天注射生理盐水的对照组动物。在注射可卡因后的前30分钟，N-ACC中的可卡因和DA浓度达到最高水平。10d和30d慢性动物的可卡因最大浓度分别为186%和156%，而DA的最大浓度分别比急性对照组动物的最大值高264%和216%。结果表明，长期服用可卡因后观察到的逆转耐受效应可能部分是由于可卡因浓度增加所致。此外，长期服用可卡因(在10天或30天内)增加了在激发注射后血浆中检测到的可卡因浓度高于对照水平。慢性动物大脑中可卡因浓度的增加显然是由于血浆中可卡因浓度的增加。由于长期服用可卡因，外周发生了生理变化，增加了血浆中的可卡因浓度，增加了大脑中的细胞外可卡因水平，并增加了N-ACC中细胞外DA的浓度。
Chronic cocaine administration produces significant increases in cocaine-induced locomotor activity and stereotypy. In vivo microdialysis procedures were used to monitor extracellular dopamine (DA) and cocaine concentrations in the nucleus accumbens (N ACC) and cocaine concentrations in plasma of animals that received chronic or acute cocaine treatments. Following a cocaine challenge injection, concentrations of both cocaine and DA increased to significantly higher levels over time in animals that had received daily cocaine injections for 10 or 30 days than in control animals that received daily injections of saline. Concentrations of cocaine and DA in the N ACC reached maximum levels in the first 30 min following a challenge injection of cocaine. The maximum cocaine concentrations of 10- and 30-day chronic animals were, respectively, 186% and 156%, whereas the maximum DA concentrations were 264% and 216% above the maximum values observed in acute control animals. The results indicate that reverse tolerance effects observed following chronic cocaine administration may in part be accounted for by increased cocaine concentrations. Furthermore, chronic cocaine administration (over a 10- or 30-day period) increased the concentration of cocaine detected in plasma above control levels following a challenge injection. The increase in brain concentrations of cocaine in chronic animals is apparently due to increased concentrations of cocaine in plasma. A physiological change occurs in the periphery as a result of chronic cocaine administration that increases cocaine concentrations in plasma, increases extracellular cocaine levels in the brain, and increases the extracellular concentration of DA in the N ACC.