Svensson T H, Mathé J M, Nomikos G G, Schilström B
Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
Amino Acids. 1998;14(1-3):51-6. doi: 10.1007/BF01345242.
The putative role of non-NMDA excitatory amino acid (EAA) receptors in the ventral tegmental area (VTA) for the increase in dopamine (DA) release in the nucleus acumbens (NAC) and the behavioural stimulation induced by systemically administered dizocilpine (MK-801) was investigated. Microdialysis was utilized in rats with probes in the VTA and NAC. The VTA was perfused with the AMPA and kainate receptor antagonist CNQX (0.3 or 1.0 mM) or vehicle and dialysates from the NAC were analyzed with high-performance liquid chromatography for DA. Forty min after onset of CNQX or vehicle perfusion of the VTA MK-801 (0.1 mg/kg) was injected subcutaneously (s.c.). Subsequently, typical MK-801 induced behaviours were assessed. The MK-801 induced hyperlocomotion was associated with a 50% increase of DA levels in NAC dialysates. Both the MK-801 evoked hyperlocomotion and DA release in the NAC were effectively antagonized by CNQX perfusion of the VTA. However, by itself the CNQX or vehicle perfusion of the VTA did not affect DA levels in NAC or the rated behaviours. The results indicate that MK-801 induced hyperlocomotion and increased DA release in the NAC are largely elicited within the VTA via activation of non-NMDA EAA receptors, tentatively caused by locally increased EAA release. In contrast, the enhanced DA output in the NAC induced by systemic nicotine (0.5 mg/kg s.c.) was not antagonized by intra VTA infusion of CNQX (0.3 or 1.0 mM), but instead by infusion of the NMDA receptor antagonist AP-5 (0.3 or 1.0 mM) into the VTA, which by itself did not alter DA levels in the NAC. Thus, the probably indirect, EAA mediated activation of the mesolimbic DA neurons in the VTA by MK-801 and nicotine, respectively, seems to be mediated via different glutamate receptor subtypes.
研究了腹侧被盖区（VTA）中非NMDA兴奋性氨基酸（EAA）受体对伏隔核（NAC）中多巴胺（DA）释放增加以及全身给予地佐环平（MK-801）所诱导的行为刺激的假定作用。在大鼠的VTA和NAC中植入探针，利用微透析技术进行研究。向VTA灌注AMPA和海人藻酸受体拮抗剂CNQX（0.3或1.0 mM）或溶剂，并用高效液相色谱法分析来自NAC的透析液中的DA。在开始向VTA灌注CNQX或溶剂40分钟后，皮下注射（s.c.）MK-801（0.1 mg/kg）。随后，评估典型的MK-801诱导的行为。MK-801诱导的运动亢进与NAC透析液中DA水平增加50%相关。VTA灌注CNQX可有效拮抗MK-801诱发的NAC运动亢进和DA释放。然而，单独的VTA灌注CNQX或溶剂并不影响NAC中的DA水平或行为评分。结果表明，MK-801诱导的运动亢进和NAC中DA释放增加主要是通过激活VTA内的非NMDA EAA受体引起的，推测是由局部EAA释放增加所致。相比之下，全身给予尼古丁（0.5 mg/kg s.c.）诱导的NAC中DA输出增强并未被VTA内注入CNQX（0.3或1.0 mM）所拮抗，而是被向VTA内注入NMDA受体拮抗剂AP-5（0.3或1.0 mM）所拮抗，而单独注入AP-5并不会改变NAC中的DA水平。因此，MK-801和尼古丁分别对VTA中中脑边缘DA神经元的可能间接的、EAA介导的激活似乎是通过不同的谷氨酸受体亚型介导的。
