Herberg L J, Stephens D N, Franklin K B
Pharmacol Biochem Behav. 1976 May;4(5):575-82. doi: 10.1016/0091-3057(76)90200-8.
Investigation of the role of noradrenaline (NA) and dopamine (DA) in self-stimulation showed that d-amphetamine (which releases more DA than does l-amphetamine, but not more NA) was much more effective than l-amphetamine in enhancing self-stimulation of NA sites in the locus coeruleus and near-lateral hypothalamus. In DA sites in the substantia nigra and far-lateral hypothalamus the effects of the 2 isomers were confirmed to be more nearly equal. Thymoxamine HCl (10 mg/kg IP), a specific alpha-adrenergic receptor blocker, depressed self-stimulation at all sites, but significantly more severely at DA sites. Thus the drugs most effective in influencing self-stimulation at a particular site were those acting predominantly on the unstimulated system. These findings were interpreted in terms of a hypothesis that DA and NA play complementary roles in self-stimulation and that both are essential; or, more specifically, that DA pathways, implicated in other motivational activites, contribute to a state of drive or arousal necessary for self-stimulation; while response-contingent noradrenergic activity (elicited by the electrodes directly via a transsynaptic route) mediates reinforcement. Further predictions from this hypothesis were tested as follows: (1) Direct pharmacological stimulants of adrenergic alpha-receptors should disrupt self-stimulation by acting randomly on the reinforcement system and disrupting response-reward contingencies; this was confirmed by the finding that the alpha-receptor stimulant clonidine HCl (0.05 mg/kg) depressed self-stimulation at all sites tested. (2) Drect stimulants of DA receptors should enhance self-stimulation of NA sites by augmenting dopaminergic motivational activity; but in rats with DA electrodes, noncontingent stimulation of DA receptors would also impose similar noncontingent activity on the transsynaptic noradrenergic reinforcement pathways and thus depress self-stimulation; this was confirmed by the finding that apomorphine (0.3-1.0 mg/kg) was strongly stimulant for NA electrodes but strongly depressant for DA electrodes, and that the degree and direction of these effects was highly correlated with the differential effects of d- l-amphetamine (rho = .65, p less than 0.01). Neither effect of apomorphine depended on the occurrence of motor stereotypy. These results can be interpreted in terms of 2-component models for self-stimulation, with the predominant transmitter of the drive component being identified as DA and that g the reinforcing component as NA.
对去甲肾上腺素（NA）和多巴胺（DA）在自我刺激中所起作用的研究表明，右旋苯丙胺（其释放的DA比左旋苯丙胺多，但释放的NA不多）在增强蓝斑和下丘脑外侧附近NA位点的自我刺激方面比左旋苯丙胺有效得多。在黑质和下丘脑最外侧的DA位点，两种异构体的作用被证实更为接近。盐酸噻吗洛尔（10毫克/千克，腹腔注射），一种特异性α-肾上腺素能受体阻滞剂，会抑制所有位点的自我刺激，但在DA位点抑制作用明显更严重。因此，在特定位点对自我刺激影响最有效的药物是那些主要作用于未受刺激系统的药物。这些发现是根据以下假设来解释的：DA和NA在自我刺激中起互补作用，且二者都是必不可少的；或者更具体地说，与其他动机活动有关的DA通路有助于产生自我刺激所需的驱力或唤醒状态；而与反应相关的去甲肾上腺素能活动（由电极直接通过跨突触途径引发）介导强化作用。从该假设得出的进一步预测通过以下方式进行了检验：（1）肾上腺素能α受体的直接药理兴奋剂应通过随机作用于强化系统并破坏反应-奖励的偶然性来干扰自我刺激；盐酸可乐定（0.05毫克/千克）在所有测试位点均能抑制自我刺激，这一发现证实了该预测。（2）DA受体的直接兴奋剂应通过增强多巴胺能动机活动来增强NA位点的自我刺激；但在植入DA电极的大鼠中，对DA受体的非偶然性刺激也会给跨突触去甲肾上腺素能强化通路带来类似的非偶然性活动，从而抑制自我刺激；阿扑吗啡（0.3 - 1.0毫克/千克）对NA电极有强烈的刺激作用，但对DA电极有强烈的抑制作用，且这些作用的程度和方向与右旋-左旋苯丙胺的差异作用高度相关（相关系数ρ = 0.65，p小于0.01），这一发现证实了该预测。阿扑吗啡的两种作用均不依赖于运动刻板行为的发生。这些结果可以用自我刺激的双成分模型来解释，驱力成分的主要递质被确定为DA，而强化成分的主要递质被确定为NA。
