Hypersensitivity of nucleus accumbens neurons to methamphetamine and dopamine following repeated administrations of methamphetamine
Hypersensitivity of nucleus accumbens neurons to methamphetamine and dopamine following repeated administrations of methamphetamine
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DOI：
10.1111/j.1749-6632.1996.tb17437.x
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发表时间：
1996-01-01
期刊：
影响因子：
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通讯作者：
Sasa, M
中科院分区：
文献类型：
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作者：
Amano, T;Matsubayashi, H;Sasa, M
已知甲基苯丙胺（MAP）滥用可诱导人类逆转耐受。电生理研究，以阐明多巴胺（DA）受体的敏感性，DA和MAP反复管理后撤药后的时间相关性变化。MAP（5 mg/kg）或生理盐水（1 ml/kg）腹腔注射，每日1次，连续5d。在水合氯醛麻醉下，用沿着七管微量吸管的玻璃微电极记录MAP给药5天的大鼠延髓核（Acc）的单个神经元活动。每个桶分别装有DA、MAP、氟哌啶醇、谷氨酸和NaCl。将药物微电泳应用于从丘脑束旁核（Pf）接收输入的Acc神经元的紧邻区域。在盐水处理的大鼠中，20-40 nA剂量的DA或MAP的离子电渗应用抑制由Pf刺激和谷氨酸诱导的放电引起的尖峰：DA和MAP的EC 50分别为23.8和23.2 nA。在24-30小时后，最后MAP管理，然而，DA和MAP对Pf刺激和谷氨酸诱导的Acc神经元放电的抑制作用不太明显，比盐水处理的动物。此外，自发放电增强氟哌啶醇应用。在给药后第5天，DA或MAP对Acc神经元的抑制作用明显大于生理盐水组。给药后第10天，DA或MAP对Acc神经元的抑制与对照组相当。这些结果表明，MAP重复给药分别在给药后24-30小时和第5天诱导Acc神经元对DA和MAP的低敏感性和超敏感性。
Methamphetamine (MAP) abuse is known to induce reverse tolerance in humans. Electrophysiological studies were performed to elucidate time-related changes in dopamine (DA) receptor sensitivities to DA and MAP after withdrawal following repeated MAP administrations. MAP (5 mg/kg) or physiological saline (1 ml/kg) was injected ip to rats once daily for 5 days. Single neuronal activities of nucleus accumbens (Acc) of 5-day MAP-administrated rats were extracellularly recorded with a glass microelectrode attached along a seven-barreled micropipette under chloral hydrate anesthesia. Each barrel was respectively filled with DA, MAP, haloperidol, glutamate and NaCl. Drugs were microiontophoretically applied to the immediate vicinity of Acc neurons receiving inputs from the parafascicular nucleus (Pf) of thalamus. Spikes elicited by Pf stimulation-and glutamate-induced firing were inhibited by iontophoretic application of either DA or MAP at doses of 20-40 nA in the saline-treated rats: EC50 for DA and MAP were 23.8 and 23.2 nA, respectively. At 24-30 hr after the final MAP administration, however, the inhibitory effects of both DA and MAP on Pf stimulation-and glutamate-induced firing of Acc neurons were less pronounced than those in the saline-treated animals. Furthermore, spontaneous firing was enhanced during haloperidol application. On day 5 postadministration, the inhibition of Acc neurons by DA or MAP was significantly more marked than that of saline-treated animals. On day 10 postadministration, the inhibition of Acc neurons by DA or MAP was comparable to that in controls. These results indicate that repeated administrations with MAP induce hyposensitivity and hypersensitivity of Acc neurons to DA and MAP at 24-30 hr and on day 5 postadministration, respectively.