Age-dependent effects of kappa-opioid receptor stimulation on cocaine-induced stereotyped behaviors and dopamine overflow in the caudate-putamen: an in vivo microdialysis study.
Age-dependent effects of kappa-opioid receptor stimulation on cocaine-induced stereotyped behaviors and dopamine overflow in the caudate-putamen: an in vivo microdialysis study.
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DOI：
10.1016/j.neuroscience.2010.04.052
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发表时间：
2010-08-11
期刊：
影响因子：
3.3
通讯作者：
McDougall, S. A.
中科院分区：
文献类型：
--
作者：
Cortez, A. M.;Charntikov, S.;Der-Ghazarian, T.;Horn, L. R.;Crawford, C. A.;McDougall, S. A.
κ-阿片受体刺激减弱了精神兴奋剂诱导的成年大鼠尾壳核（CPu）和延髓核细胞外多巴胺的增加，同时减少了可卡因诱导的运动活动和刻板行为。因为κ-阿片受体激动剂（例如，U 50，488或U69，593）经常以矛盾的方式影响断奶前大鼠的行为，本研究的目的是确定κ-阿片受体刺激是否根据年龄差异影响CPu中的多巴胺能功能。在体内微透析用于确定是否U 50，488（5毫克/公斤）减弱可卡因诱导的多巴胺溢出在背侧CPu在出生后第17天（PD）和PD 85。在显微注射实验中，在向CPu双侧输注溶剂或U 50，488（每侧1.6或6.4 µg）后，在成年和断奶前大鼠中评估可卡因诱导的刻板行为。结果显示，U 50，488减弱了PD 85时可卡因诱导的CPu多巴胺溢出增加，而相同剂量的U 50，488在PD 17时未改变多巴胺透析液水平。在这两个年龄段，coconut也增加了刻板行为（重复的运动动作，行为强度评分和离散行为），但成年大鼠似乎表现出比年轻动物更强烈的刻板反应。与微透析研究结果一致，双侧输注U 50，488到背侧CPu减少了成年大鼠可卡因诱导的刻板行为，同时使断奶前大鼠的行为不受影响。这些结果表明，在CPu的κ-阿片/多巴胺相互作用的神经机制是不完全成熟的断奶前期间。这种功能成熟的缺乏可以解释为什么κ-阿片受体激动剂经常在年轻和成年大鼠中诱导不同的行为效应。
κ-Opioid receptor stimulation attenuates psychostimulant-induced increases in extracellular dopamine in the caudate-putamen (CPu) and nucleus accumbens of adult rats, while reducing cocaine-induced locomotor activity and stereotyped behaviors. Because κ-opioid receptor agonists (e.g., U50,488 or U69,593) often affect the behavior of preweanling rats in a paradoxical manner, the purpose of the present study was to determine whether κ-opioid receptor stimulation differentially affects dopaminergic functioning in the CPu depending on age. In vivo microdialysis was used to determine whether U50,488 (5 mg/kg) attenuates cocaine-induced dopamine overflow in the dorsal CPu on postnatal day (PD) 17 and PD 85. In the microinjection experiment, cocaine-induced stereotyped behaviors were assessed in adult and preweanling rats after bilateral infusions of vehicle or U50,488 (1.6 or 6.4 µg per side) into the CPu. Results showed that U50,488 attenuated the cocaine-induced increases in CPu dopamine overflow on PD 85, while the same dose of U50,488 did not alter dopamine dialysate levels on PD 17. Cocaine also increased stereotyped behaviors (repetitive motor movements, behavioral intensity scores, and discrete behaviors) at both ages, but adult rats appeared to exhibit more intense stereotypic responses than the younger animals. Consistent with the microdialysis findings, bilateral infusions of U50,488 into the dorsal CPu decreased the cocaine-induced stereotypies of adult rats, while leaving the behaviors of preweanling rats unaffected. These results suggest that the neural mechanisms underlying κ-opioid/dopamine interactions in the CPu are not fully mature during the preweanling period. This lack of functional maturity may explain why κ-opioid receptor agonists frequently induce different behavioral effects in young and adult rats.
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影响因子：
5
作者：
Bolanos, CA;Garmsen, GM;McDougall, SA
通讯作者：
McDougall, SA
影响因子：
2.2
作者：
ABRAMS, DR;BRUNO, JP
通讯作者：
BRUNO, JP
DOI：
10.1016/s0165-3806(99)00153-4
发表时间：
2000-01-03
期刊：
DEVELOPMENTAL BRAIN RESEARCH
影响因子：
--
作者：
Collins, RL;Zavala, AR;McDougall, SA
通讯作者：
McDougall, SA
影响因子：
2.3
作者：
Ikemoto, S;Witkin, BM
通讯作者：
Witkin, BM
影响因子：
2.9
作者：
BORDI, F;CARR, KD;MELLER, E
通讯作者：
MELLER, E