首页> 美国卫生研究院文献>other >AGE-DEPENDENT EFFECTS OF κ-OPIOID RECEPTOR STIMULATION ON COCAINE-INDUCED STEREOTYPED BEHAVIORS AND DOPAMINE OVERFLOW IN THE CAUDATE-PUTAMEN: AN IN VIVO MICRODIALYSIS STUDY
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AGE-DEPENDENT EFFECTS OF κ-OPIOID RECEPTOR STIMULATION ON COCAINE-INDUCED STEREOTYPED BEHAVIORS AND DOPAMINE OVERFLOW IN THE CAUDATE-PUTAMEN: AN IN VIVO MICRODIALYSIS STUDY

机译:κ-阿片受体受体刺激对可卡因诱导的甲状腺素诱导的刻板行为和多巴胺溢出的年龄依赖性作用:体内微透析研究

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摘要

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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