Hitzemann R, Curell J, Hom D, Loh H
Neuropharmacology. 1982 Oct;21(10):1005-11. doi: 10.1016/0028-3908(82)90114-9.
The effects of acute naloxone administration on d-amphetamine- and apomorphine-induced behavior were studied. Naloxone, in doses of 0.3-10 mg/kg (s.c.), antagonized the increase in ambulation and rearing induced by 1 mg/kg of d-amphetamine. When the dose of d-amphetamine was increased to 3 mg/kg, naloxone (3 mg/kg) antagonized only the increase in rearing activity. No dose (0.3-10 mg/kg, s.c.) of naloxone significantly affected d-amphetamine- or apomorphine-induced stereotyped activity. Naloxone (3 mg/kg) significantly augmented the apomorphine (1 mg/kg, s.c.)-induced increase in ambulation but attenuated the apomorphine (0.3 mg/kg)-induced increase in rearing activity. Naloxone (3 mg/kg) or apomorphine (0.03 mg/kg) significantly decreased the ambulation and rearing induced by a novel environment. In combination and in these doses, naloxone and apomorphine produced an additive effect on these behaviors. The neurochemical mechanisms by which naloxone affects d-amphetamine- and apomorphine-induced behavior were investigated. Naloxone (10(-6) M) had no significant effect on [3H]spiroperidol binding in either the caudate nucleus or nucleus accumbens except for a modest inhibition (24%) of both the Km and Bmax in the accumbens microsomal fraction. Similarly, naloxone (10(-6) M) had no significant effect on [3H]dopamine(DA) uptake into either brain region nor did naloxone alter the d-amphetamine-inhibition of uptake. Using perfused tissue slices, naloxone (10(-6)-10(-5) M) significantly attenuated the increase in [3H]DA release induced by d-amphetamine (10(-5) M) in both brain regions. Naloxone (1 mg/kg) had no significant effect on DA or dihydroxyphenyl-acetic acid (DOPAC) levels or on the DA/DOPAC ratio in the caudate nucleus or nucleus accumbens. However, naloxone did reverse the marked increases in the DA-DOPAC ratio induced by d-amphetamine (1 mg/kg) in both brain regions.
研究了急性给予纳洛酮对右旋苯丙胺和阿扑吗啡诱导行为的影响。剂量为0.3 - 10mg/kg（皮下注射）的纳洛酮可拮抗1mg/kg右旋苯丙胺诱导的走动和竖毛增加。当右旋苯丙胺剂量增加到3mg/kg时，纳洛酮（3mg/kg）仅拮抗竖毛活动的增加。任何剂量（0.3 - 10mg/kg，皮下注射）的纳洛酮对右旋苯丙胺或阿扑吗啡诱导的刻板活动均无显著影响。纳洛酮（3mg/kg）显著增强了阿扑吗啡（1mg/kg，皮下注射）诱导的走动增加，但减弱了阿扑吗啡（0.3mg/kg）诱导的竖毛活动增加。纳洛酮（3mg/kg）或阿扑吗啡（0.03mg/kg）显著减少了新环境诱导的走动和竖毛。以这些剂量联合使用时，纳洛酮和阿扑吗啡对这些行为产生相加作用。研究了纳洛酮影响右旋苯丙胺和阿扑吗啡诱导行为的神经化学机制。纳洛酮（10⁻⁶M）对尾状核或伏隔核中[³H]螺哌啶结合无显著影响，除了对伏隔核微粒体部分的Km和Bmax有适度抑制（24%）。同样，纳洛酮（10⁻⁶M）对两个脑区的[³H]多巴胺（DA）摄取均无显著影响，纳洛酮也未改变右旋苯丙胺对摄取的抑制作用。使用灌注组织切片，纳洛酮（10⁻⁶ - 10⁻⁵M）显著减弱了两个脑区中右旋苯丙胺（10⁻⁵M）诱导的[³H]DA释放增加。纳洛酮（1mg/kg）对尾状核或伏隔核中的DA或二羟基苯乙酸（DOPAC）水平以及DA/DOPAC比值无显著影响。然而，纳洛酮确实逆转了两个脑区中右旋苯丙胺（1mg/kg）诱导的DA - DOPAC比值的显著增加。
