Sinden J D, Atrens D M
Eur J Pharmacol. 1982 Dec 24;86(2):237-46. doi: 10.1016/0014-2999(82)90321-1.
Dopaminergic and noradrenergic inhibition of lateral hypothalamic self-stimulation was investigated in a new signalled, discrete-trials shuttle-box paradigm. The differential inhibitory effects of drugs and stimulation frequency reductions within small blocks of trials differentiate reward inhibition from a variety of performance deficits. They further differentiate among the deficits produced by fatigue, sedation, dyskinesias, akinesia and sensory disruption. Pimozide's selective inhibition of the first response within each block of trials shows that its inhibition of self-stimulation is not due to either an inhibition of reward or to a general performance deficit. Instead, it suggests that pimozide specifically inhibits the initiation of motor responding. Pimozide-induced akinesia appears to be partly reversible by hypothalamic stimulation. Thus the pimozide data do not support a role for dopamine in mediating brain-stimulation reward. Since the inhibitory effects of clonidine were very similar to those of pimozide, it is suggested that clonidine also produces a stimulation-reversible akinesia. Thus the clonidine data do not support a role for noradrenaline in mediating brain-stimulation reward. LU 5-003, which selectively inhibits the presynaptic reuptake of noradrenaline, inhibited self-stimulation in almost exactly the same way as did reducing reward by reducing stimulation frequency. These data do support a primary role for noradrenaline in mediating brain-stimulation reward. However, it is suggested that LU 5-003 inhibits self-stimulation, not by inhibiting reward, but by enhancing reward and making the electrical stimulation superfluous.
在一种新的有信号提示、离散试验穿梭箱范式中，研究了多巴胺能和去甲肾上腺素能对下丘脑外侧自我刺激的抑制作用。在小试验组内，药物的不同抑制作用以及刺激频率降低所产生的不同抑制效果，将奖赏抑制与各种行为表现缺陷区分开来。它们还能进一步区分由疲劳、镇静、运动障碍、运动不能和感觉障碍所导致的行为缺陷。匹莫齐特在每组试验中对首次反应的选择性抑制表明，其对自我刺激的抑制作用既不是由于对奖赏的抑制，也不是由于一般的行为表现缺陷。相反，这表明匹莫齐特特异性地抑制运动反应的启动。下丘脑刺激似乎能部分逆转匹莫齐特诱导的运动不能。因此，匹莫齐特的数据不支持多巴胺在介导脑刺激奖赏中起作用。由于可乐定的抑制作用与匹莫齐特非常相似，因此有人提出可乐定也会产生刺激可逆性运动不能。因此，可乐定的数据不支持去甲肾上腺素在介导脑刺激奖赏中起作用。LU 5-003选择性抑制去甲肾上腺素的突触前再摄取，其抑制自我刺激的方式几乎与通过降低刺激频率来减少奖赏的方式完全相同。这些数据确实支持去甲肾上腺素在介导脑刺激奖赏中起主要作用。然而，有人提出LU 5-003抑制自我刺激，不是通过抑制奖赏，而是通过增强奖赏并使电刺激变得多余。
