Kiyatkin E A, Rebec G V
Department of Psychology, Indiana University, Bloomington 47405, USA.
Brain Res. 1997 Oct 10;771(1):14-24. doi: 10.1016/s0006-8993(97)00689-6.
When administered systemically to ambulant animals, amphetamine (AMPH) has both excitatory and inhibitory effects on single-unit activity in the neostriatum and nucleus accumbens. To determine the extent to which these results reflect a direct action of the drug, AMPH was applied iontophoretically to neostriatal and accumbal neurons under naturally occurring behavioral conditions. AMPH dose-dependently (5-40 nA) inhibited the vast majority of spontaneously active units. The inhibition, which was evident at low ejection currents (5-10 nA), had relatively short onset (4-12 s) and offset (6-24 s) latencies, and was positively correlated with basal firing rate. Even stronger dose-dependent inhibitory responses were recorded when neurons having no or a very low rate of spontaneous activity were tonically activated by continuous, low-current applications of glutamate (Glu). Systemic injection of either SCH-23390 (0.1 mg/kg) or haloperidol (0.2 mg/kg), relatively selective D1 and D2 receptor antagonists, respectively, blocked the AMPH-induced inhibition. Prolonged AMPH iontophoresis (2-3 min; 5-30 nA) inhibited both spontaneous impulse activity and Glu-induced excitations, resulting in a complete blockade of the Glu response at relatively high AMPH ejection currents (> or = 20 nA). Taken together, these results suggest that although dopamine is largely responsible for the inhibitory effects of iontophoretic AMPH, dopamine alone cannot account for the complex response of neostriatal and accumbal neurons to systemic AMPH administration.
当对活动的动物进行全身给药时，苯丙胺（AMPH）对新纹状体和伏隔核中的单单位活动既有兴奋作用又有抑制作用。为了确定这些结果在多大程度上反映了药物的直接作用，在自然行为条件下，将AMPH通过离子电泳法应用于新纹状体和伏隔核神经元。AMPH剂量依赖性地（5-40 nA）抑制了绝大多数自发活动的单位。这种抑制在低喷射电流（5-10 nA）时就很明显，起始潜伏期相对较短（4-12秒），抵消潜伏期也较短（6-24秒），并且与基础放电率呈正相关。当通过持续低电流应用谷氨酸（Glu）使无自发活动或自发活动率极低的神经元被强直性激活时，记录到了更强的剂量依赖性抑制反应。分别系统性注射相对选择性的D1和D2受体拮抗剂SCH-23390（0.1 mg/kg）或氟哌啶醇（0.2 mg/kg），可阻断AMPH诱导的抑制作用。长时间的AMPH离子电泳（2-3分钟；5-30 nA）抑制了自发冲动活动和Glu诱导的兴奋，在相对较高的AMPH喷射电流（≥20 nA）时导致Glu反应完全被阻断。综上所述，这些结果表明，虽然多巴胺在很大程度上负责离子电泳AMPH的抑制作用，但仅多巴胺不能解释新纹状体和伏隔核神经元对全身给予AMPH的复杂反应。
