Del Arco A, Mora F, Mohammed A H, Fuxe K
Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.
J Neural Transm (Vienna). 2007 Feb;114(2):185-93. doi: 10.1007/s00702-006-0533-3. Epub 2006 Aug 8.
The aim of the present study was to investigate the effects of stimulation of D2 receptors in the prefrontal cortex (PFC) on spontaneous motor activity and the hyperactivity induced by the psychomimetic phencyclidine (PCP). In addition, the effects of prefrontal D2 stimulation under PCP treatment on dialysate concentrations of acetylcholine, choline, dopamine, DOPAC and HVA in the nucleus accumbens were also investigated. Sprague-Dawley male rats were implanted with guide cannulae to perform bilateral injections into the medial PFC of the D2 agonist quinpirole (1.5 and 5 microg/side). Horizontal and vertical spontaneous motor activity and the motor activity induced by systemic injections of the PCP (5 mg/kg i.p.) were monitored in the open field. PFC injections of quinpirole (1.5 and 5 microg/side) significantly decreased horizontal and vertical spontaneous motor activity in a dose-related manner. These effects were blocked by the D2 antagonist raclopride (5 microg/side). Microinjections of quinpirole (1.5 and 5 microg/side) into the PFC also significantly attenuated the hyperactivity produced by PCP (5 mg/kg i.p.). PCP also increased dialysate concentrations of acetylcholine, and dopamine metabolites in the nucleus accumbens. These increases were also reduced by injections of quinpirole (5 microg/side) into the PFC. These results suggest that the stimulation of prefrontal D2 receptors plays an inhibitory role in regulating spontaneous and PCP-induced motor activity and also in the neurochemical changes produced by PCP in the nucleus accumbens.
本研究的目的是调查刺激前额叶皮质（PFC）中的D2受体对自发运动活动以及由拟精神病药物苯环利定（PCP）诱导的多动的影响。此外，还研究了在PCP治疗下前额叶D2刺激对伏隔核中乙酰胆碱、胆碱、多巴胺、3,4-二羟基苯乙酸（DOPAC）和高香草酸（HVA）透析液浓度的影响。将Sprague-Dawley雄性大鼠植入引导套管，以便向内侧PFC双侧注射D2激动剂喹吡罗（1.5和5微克/侧）。在旷场中监测水平和垂直自发运动活动以及全身注射PCP（5毫克/千克腹腔注射）诱导的运动活动。向PFC注射喹吡罗（1.5和5微克/侧）以剂量相关的方式显著降低了水平和垂直自发运动活动。这些作用被D2拮抗剂雷氯必利（5微克/侧）阻断。向PFC微量注射喹吡罗（1.5和5微克/侧）也显著减弱了PCP（5毫克/千克腹腔注射）产生的多动。PCP还增加了伏隔核中乙酰胆碱和多巴胺代谢物的透析液浓度。向PFC注射喹吡罗（5微克/侧）也降低了这些增加。这些结果表明，刺激前额叶D2受体在调节自发和PCP诱导的运动活动以及PCP在伏隔核中产生的神经化学变化中起抑制作用。
