Giménez-Llort Lydia, Wang Fu Hua, Ogren Sven Ove, Ferré Sergi
Department of Neuroscience, Karolinska Institute, 17177 Stockholm, Sweden.
Neuropsychopharmacology. 2002 Jun;26(6):737-43. doi: 10.1016/S0893-133X(01)00411-0.
Dopaminergic neurotransmission has been implicated in the motor activating effects induced by the local infusion of NMDA in the ventral hippocampus (VH). The nucleus accumbens and the ventral tegmental area (VTA) have been proposed to be the main loci where dopamine is acting as a positive modulator of the VH NMDA receptor-mediated motor activating effects. However, the existence of a relatively high dopamine innervation and dopamine receptor density in the VH suggests the possibility of local dopamine/NMDA receptor interactions. This hypothesis was tested by studying the effects of the bilateral local VH infusion of NMDA (0.05, 0.1, 0.5 and 1.0 microg/side), the dopamine D1/D5 receptor antagonist SCH 23390 (1 microg/side) and the dopamine D2 receptor antagonist raclopride (1 and 5 microg/side). Neither SCH 23390 nor raclopride induced any significant change in motor activity compared with the vehicle control group, but both compounds significantly antagonized the motor activation induced by NMDA. SCH 23390 (1 microg/side) was more potent that raclopride (minimal effective dose: 5 microg/side). These results demonstrate the existence of a strong tonic facilitating effect of dopamine, acting preferentially at dopamine D1/D5 receptors, on NMDA receptor-mediated effects in the VH.
多巴胺能神经传递与腹侧海马(VH)局部注射N-甲基-D-天冬氨酸(NMDA)所诱导的运动激活效应有关。伏隔核和腹侧被盖区(VTA)被认为是多巴胺作为VH中NMDA受体介导的运动激活效应的正向调节剂发挥作用的主要位点。然而,VH中相对较高的多巴胺神经支配和多巴胺受体密度表明存在局部多巴胺/NMDA受体相互作用的可能性。通过研究双侧局部VH注射NMDA(0.05、0.1、0.5和1.0微克/侧)、多巴胺D1/D5受体拮抗剂SCH 23390(1微克/侧)和多巴胺D2受体拮抗剂雷氯必利(1和5微克/侧)的作用来验证这一假设。与溶剂对照组相比,SCH 23390和雷氯必利均未引起运动活动的任何显著变化,但两种化合物均显著拮抗了NMDA诱导的运动激活。SCH 23390(1微克/侧)比雷氯必利更有效(最小有效剂量:5微克/侧)。这些结果表明,多巴胺对VH中NMDA受体介导的效应存在强烈的紧张性促进作用,且优先作用于多巴胺D1/D5受体。