Riffee W H, Gerald M C
Psychopharmacology (Berl). 1977 Jan 31;51(2):175-9. doi: 10.1007/BF00431736.
The i.v. pentylenetetrazol seizure threshold was increased by 2.5 mg/kg and decreased by 15 mg/kg of a single (+)-amphetamine dose. After 7 consecutive days of amphetamine administration, tolerance developed to the decrease but not to the increase in seizure threshold. At 12--48 h after the last dose of 2.5 mg/kg seizure threshold was decreased, and at 36--48 h after the last dose of 15 mg/kg seizure threshold was increased. After acute and chronic administration of (+)-amphetamine (2.5 mg/kg) endogenous concentrations of whole brain dopamine (DA) were increased and returned to normal levels during the withdrawal period (12--48 h); endogenous norepinephrine (NE) levels were unchanged by acute and chronic drug treatment and during withdrawal. The rates of DA and NE synthesis were increased by chronic amphetamine administration at 24--48 h after drug withdrawal. An acute dose of (+)-amphetamine (15 mg/kg) decreased endogenous levels of DA and NE; normal levels of DA were detected with chronic drug treatment and during withdrawal, with NE remaining slightly depressed. The rates of synthesis of DA and NE were increased by acute and chronic amphetamine treatment and returned to normal 24--48 h after withdrawal. The rebound reversal in seizure threshold after (+)-amphetamine withdrawal suggests an abstinence syndrome that may be interpreted as evidence for the development of physical dependence to (+)-amphetamine after chronic drug administration.
静脉注射戊四氮惊厥阈值在单次给予2.5毫克/千克（+）-苯丙胺后升高，而在给予15毫克/千克后降低。连续7天给予苯丙胺后，耐受性发展至对惊厥阈值降低的情况，但对升高的情况则未产生耐受性。在最后一剂2.5毫克/千克后的12至48小时惊厥阈值降低，而在最后一剂15毫克/千克后的36至48小时惊厥阈值升高。急性和慢性给予（+）-苯丙胺（2.5毫克/千克）后，全脑多巴胺（DA）的内源性浓度升高，并在戒断期（12至48小时）恢复至正常水平；急性和慢性药物治疗以及戒断期间，内源性去甲肾上腺素（NE）水平未发生变化。药物戒断后24至48小时，慢性给予苯丙胺会增加DA和NE的合成速率。一剂急性（+）-苯丙胺（15毫克/千克）会降低DA和NE的内源性水平；慢性药物治疗及戒断期间可检测到正常的DA水平，而NE仍略有降低。急性和慢性苯丙胺治疗会增加DA和NE的合成速率，并在戒断后24至48小时恢复正常。（+）-苯丙胺戒断后惊厥阈值的反弹逆转表明存在一种戒断综合征，这可能被解释为慢性药物给药后对（+）-苯丙胺产生身体依赖的证据。
