Boivin Gregory A, Beninger Richard J
Department of Psychology, Queen's University, Kingston, Ontario, Canada.
Behav Neurosci. 2008 Apr;122(2):377-84. doi: 10.1037/0735-7044.122.2.377.
AMPA receptor antagonists disrupt avoidance responding, but their day-to-day effect on this behavior has not been elucidated. This study compared the multisession effect of the AMPA/kainate receptor antagonist CNQX with that of the typical antipsychotic haloperidol on the expression of avoidance responding. Rats (N = 199) were trained to move to safety on presentation of a tone in one-way active conditioned avoidance and were tested across 5 sessions. Intracerebroventricular (icv) injection of CNQX (20-min injection-test interval) produced a dose-dependent, immediate block of avoidance responding, compared with the extinction-like decline of avoidance responding produced by haloperidol (intraperitoneal [ip], 60-min injection-test interval; icv, 60 but not 20-min injection-test interval). Previous exposure to CNQX significantly reduced its efficacy, illustrating that its effects may not be specific to the conditioned safety-related stimuli that control responding in conditioned avoidance, as proposed for antidopaminergic compounds. The new multisession profile of disrupted avoidance responding illustrated by CNQX suggests different roles for glutamatergic and dopaminergic neurotransmission in conditioned avoidance responding. Results are consistent with a role for AMPA receptors in maintaining the expression of learning.
AMPA受体拮抗剂会破坏回避反应，但其对这种行为的日常影响尚未阐明。本研究比较了AMPA/海人酸受体拮抗剂CNQX与典型抗精神病药物氟哌啶醇对回避反应表达的多阶段影响。大鼠（N = 199）在单向主动条件回避中接受训练，当听到音调时移动到安全区域，并进行了5个阶段的测试。与氟哌啶醇（腹腔注射[ip]，注射-测试间隔60分钟；脑室内[icv]注射，注射-测试间隔60分钟而非20分钟）产生的类似消退的回避反应下降相比，脑室内注射CNQX（注射-测试间隔20分钟）产生了剂量依赖性的即时回避反应阻断。先前接触CNQX会显著降低其效力，这表明其作用可能不像抗多巴胺能化合物那样特异性地作用于控制条件回避反应的与条件安全相关的刺激。CNQX所显示的新的多阶段破坏回避反应模式表明谷氨酸能和多巴胺能神经传递在条件回避反应中具有不同作用。结果与AMPA受体在维持学习表达中的作用一致。
