Snoddy A M, Tessel R E
Eur J Pharmacol. 1985 Oct 22;116(3):221-8. doi: 10.1016/0014-2999(85)90156-6.
Mice trained to discriminate 1 mg/kg d-amphetamine from saline, or the selective norepinephrine uptake inhibitor, nisoxetine, from saline, cross-generalized to the alternate drug. They also generalized to 5.6 mg/kg cocaine. The cues produced by amphetamine were antagonized by the selective alpha 1-adrenoceptor antagonist, prazosin, and slightly potentiated by the selective alpha 2-adrenoceptor antagonist, yohimbine. The nisoxetine cue was also antagonized by prazosin. In contrast, the peripherally acting sympathomimetics, p-hydroxyamphetamine and phenylpropranolamine, failed to substitute for, and pimozide and propranolol failed to block, either drug cue. In addition, prazosin, at a dose that did not affect either saline-associated locomotor behavior in mice or the locomotor-activity increase produced by the dopamine uptake inhibitor, bupropion, also antagonized the locomotor stimulation produced by amphetamine and cocaine. Thus, in mice, both the cues and locomotor stimulation produced by amphetamine and cocaine appear to be at least partially mediated by central alpha 1-adrenoceptor activation secondary to increased central synaptic concentrations of norepinephrine.
经训练能区分1毫克/千克右旋苯丙胺与生理盐水，或区分选择性去甲肾上腺素摄取抑制剂尼索西汀与生理盐水的小鼠，会交叉泛化到另一种药物。它们也会泛化到5.6毫克/千克可卡因。苯丙胺产生的线索被选择性α1肾上腺素能受体拮抗剂哌唑嗪拮抗，被选择性α2肾上腺素能受体拮抗剂育亨宾轻微增强。尼索西汀线索也被哌唑嗪拮抗。相比之下，外周作用的拟交感神经药对羟基苯丙胺和苯丙醇胺不能替代药物线索，匹莫齐特和普萘洛尔也不能阻断药物线索。此外，哌唑嗪在不影响小鼠与生理盐水相关的运动行为或多巴胺摄取抑制剂安非他酮产生的运动活动增加的剂量下，也能拮抗苯丙胺和可卡因产生的运动刺激。因此，在小鼠中，苯丙胺和可卡因产生的线索及运动刺激似乎至少部分是由去甲肾上腺素中枢突触浓度增加继发的中枢α1肾上腺素能受体激活介导的。
