Sorg B A, Li N, Wu W, Bailie T M
Alcohol and Drug Abuse Program and Program in Neuroscience, Department of Veterinary and Comparative Anatomy, Pharmacology and Physiology, Stadium Way, Washington State University, Pullman, WA 99164-6520, USA.
Neuroscience. 2004;127(1):187-96. doi: 10.1016/j.neuroscience.2004.05.013.
We examined the effects of repeated stress and D1 receptor activation in the medial prefrontal cortex (mPFC) on acute-cocaine-induced locomotor activity in rats. Male rats were given 7 days of either handling (Controls) or a variety of stressors. After 8-17 days' withdrawal, rats received an intra-mPFC microinjection of the full D1 agonist, SKF 81297: 0, 0.03, 0.1 or 0.3 microg/side followed by an i.p. saline or cocaine injection (15 mg/kg, i.p.). The target sites were either the dorsal or ventral mPFC. We also divided rats into either high or low responders based on their locomotor response to an acute cocaine injection. In the dorsal PFC, low responder Control and Stress groups demonstrated an augmentation of cocaine-induced increases in activity after SKF 81297, compared with vehicle, microinjection. In contrast, high responder rats demonstrated a suppression of cocaine-induced increases in activity after intra-mPFC SFK 81297 infusion, with an apparent 10 times higher sensitivity in the Stress group. In the ventral PFC, low responder Controls showed no changes after SKF 81297 infusion, while the Stress group showed an increase in cocaine-induced activity in response to SKF 81297. In high responders given SFK 81297 into the ventral mPFC, cocaine-induced activity was suppressed in Controls, while stress pretreatment rendered animals resistant to SKF 81297 effects. These results indicate that D1 receptor activation effects in the mPFC are bidirectional depending on whether rats have a high or low locomotor response to cocaine. Further, daily stress alters the sensitivity of the mPFC to SKF 81297, which is dependent on whether the dorsal or ventral mPFC is targeted.
我们研究了内侧前额叶皮质（mPFC）中反复应激和D1受体激活对大鼠急性可卡因诱导的运动活动的影响。雄性大鼠接受7天的处理（对照组）或各种应激源。在撤药8 - 17天后，大鼠接受mPFC内微量注射完全D1激动剂SKF 81297：每侧0、0.03、0.1或0.3微克，随后腹腔注射生理盐水或可卡因（15毫克/千克，腹腔注射）。靶点部位为背侧或腹侧mPFC。我们还根据大鼠对急性可卡因注射的运动反应将其分为高反应者或低反应者。在背侧前额叶皮质，低反应者对照组和应激组在注射SKF 81297后，与注射溶媒相比，可卡因诱导的活动增加有所增强。相反，高反应者大鼠在mPFC内注射SFK 81297后，可卡因诱导的活动增加受到抑制，应激组的敏感性明显高出10倍。在腹侧前额叶皮质，低反应者对照组在注射SKF 81297后无变化，而应激组在注射SKF 81297后可卡因诱导的活动增加。在腹侧mPFC注射SFK 81297的高反应者中，对照组可卡因诱导的活动受到抑制，而应激预处理使动物对SKF 81297的作用产生抗性。这些结果表明，mPFC中D1受体激活的作用是双向的，这取决于大鼠对可卡因的运动反应是高还是低。此外，每日应激会改变mPFC对SKF 81297的敏感性，这取决于背侧或腹侧mPFC是否为靶点。
