Shah Akeel A, Sjovold Travis, Treit Dallas
Department of Psychology, University of Alberta, Edmonton, AB, Canada.
Eur J Neurosci. 2004 Jun;19(12):3393-7. doi: 10.1111/j.0953-816X.2004.03447.x.
It is well known that the mesolimbocortical dopamine pathway is highly active during periods of stress and fear. However, very little research has directly examined how dopamine receptors in this pathway influence fear-related behaviour. The present study examined the effects of selective antagonism of D(4), D(1) and D(2) dopamine receptors of the medial prefrontal cortex (MPFC) on rats' fear behaviour in the elevated plus-maze and the shock-probe burying tests. The results demonstrated that bilateral intra-MPFC infusions of the highly selective D(4) antagonist, L-745 870 (0.2, 1 or 10 nmol/0.5 microL), increased the percentage of open-arm entries and open-arm time in the elevated plus-maze test (1 nmol/0.5 microL), and decreased the duration of burying in the shock-probe test (0.2 or 1 nmol/0.5 microL). Furthermore, none of the doses of the D(4) antagonist affected measures of general activity or pain sensitivity. Intra-MPFC infusions of the D(1) antagonist, SCH-23390 (0.2 or 1 nmol/0.5 microL), or the D(2) antagonist, remoxipride (0.2, 1 or 10 nmol/0.5 microL), had no significant behavioural effects in either test. Taken together, these findings suggest that MPFC D(4) receptors may play an important role in the mediation of fear-related behaviour.
众所周知，中脑边缘皮质多巴胺通路在应激和恐惧期间高度活跃。然而，很少有研究直接考察该通路中的多巴胺受体如何影响与恐惧相关的行为。本研究考察了内侧前额叶皮质（MPFC）中D(4)、D(1)和D(2)多巴胺受体的选择性拮抗作用对大鼠在高架十字迷宫和电击探针掩埋试验中的恐惧行为的影响。结果表明，双侧MPFC内注射高选择性D(4)拮抗剂L-745 870（0.2、1或10 nmol/0.5 μL），在高架十字迷宫试验中增加了进入开放臂的百分比和在开放臂停留的时间（1 nmol/0.5 μL），并在电击探针试验中减少了掩埋持续时间（0.2或1 nmol/0.5 μL）。此外，D(4)拮抗剂的任何剂量均未影响一般活动或疼痛敏感性的测量指标。MPFC内注射D(1)拮抗剂SCH-23390（0.2或1 nmol/0.5 μL）或D(2)拮抗剂瑞莫必利（0.2、1或10 nmol/0.5 μL），在两项试验中均未产生显著的行为影响。综上所述，这些发现表明MPFC的D(4)受体可能在介导与恐惧相关的行为中起重要作用。
