Masson Sueli, Avanzi Viviane, Troncoso Ana Cristina, Brandão Marcus Lira
Laboratório de Psicobiologia, Depto de Psicologia, FFCLRP, Campus da USP, Av., Bandeirantes, 3900, 14049-901, Ribeirão Preto, São Paulo, Brazil.
Prog Neuropsychopharmacol Biol Psychiatry. 2003 Sep;27(6):935-43. doi: 10.1016/S0278-5846(03)00153-2.
Consistent evidence has shown that learning may be produced in paradigms using electrical stimulation of the inferior colliculus as unconditioned stimulus (US). Much evidence has also been provided for the involvement of dopamine in the setting up of adaptive responses to aversive states generated at this mesencephalic level. The aim of the present study was to determine whether dopaminergic mechanisms are involved in the conditioned freezing behavior and latent inhibition (LI) using either foot shocks (Experiment 1) or inferior colliculus stimulation (Experiment 2) as US and light as conditioned stimulus (CS). To this end, the authors examined the effects of the dopaminergic agonist apomorphine (AP; 0, 0.5, 1.0, and 2.0 mg/kg) and the atypical antipsychotic clozapine (CLZ 0, 1.0, 2.5, and 5.0 mg/kg) on the acquisition of conditioned freezing and LI. Rats were either simply placed in the experimental chamber non-preexposed (NPE) or preexposed (PE) to 50 light presentations. Next, they were submitted to 10 light plus foot shock (or inferior colliculus stimulation) pairings. In the testing session, conditioned freezing under the CS was measured. In both experiments, conditioned freezing was highly significant in the NPE group while previous exposure to nonreinforced light (PE) weakened the strength of the conditioning. Although weaker than that caused by foot shock/light pairings, the occurrence of freezing and LI with the use of inferior colliculus stimulation as US gives additional support to the participation of this structure in the filtering processes of relevant information to higher brain regions. The drug effects depended on whether foot shock or inferior colliculus stimulation was used as US. In Experiment 1, AP produced a dose dependent increase in conditioned freezing without changing LI. On the other hand, CLZ did not change freezing and LI. In Experiment 2 while AP did not change freezing and LI, CLZ clearly increased freezing without changing LI with the use of inferior colliculus as US. The selective effect of AP on conditioned freezing due to light/foot shocks association is consistent with the heightened attentional and cognitive functions of dopaminergic mechanisms of the mesocorticolimbic systems in the setting up of adaptive responses aimed at coping with or signaling the presence of stimuli of aversive nature. The selective effect of CLZ on conditioned freezing is due to light/IC stimulation and may also be due to the known antagonism of 5-HT(2) receptors produced by low doses of this atypical antipsychotic.
一致的证据表明，在使用电刺激下丘作为非条件刺激（US）的范式中可能会产生学习。也有许多证据表明多巴胺参与了对在这个中脑水平产生的厌恶状态建立适应性反应。本研究的目的是确定多巴胺能机制是否参与了以足部电击（实验1）或下丘刺激（实验2）作为非条件刺激、光作为条件刺激（CS）的条件性僵住行为和潜伏抑制（LI）。为此，作者研究了多巴胺能激动剂阿扑吗啡（AP；0、0.5、1.0和2.0毫克/千克）和非典型抗精神病药物氯氮平（CLZ 0、1.0、2.5和5.0毫克/千克）对条件性僵住和LI习得的影响。将大鼠简单地置于实验箱中，未预先暴露（NPE）或预先暴露（PE）于50次光刺激。接下来，使它们接受10次光加足部电击（或下丘刺激）配对。在测试阶段，测量CS下的条件性僵住。在两个实验中，NPE组的条件性僵住非常显著，而先前暴露于无强化光（PE）会削弱条件作用的强度。尽管使用下丘刺激作为非条件刺激时产生的僵住和LI比足部电击/光配对引起的要弱，但这进一步支持了该结构参与向更高脑区过滤相关信息的过程。药物效应取决于使用足部电击还是下丘刺激作为非条件刺激。在实验1中，AP使条件性僵住呈剂量依赖性增加，而不改变LI。另一方面，CLZ不改变僵住和LI。在实验2中，当使用下丘作为非条件刺激时，AP不改变僵住和LI，而CLZ明显增加僵住且不改变LI。AP对光/足部电击关联引起的条件性僵住的选择性作用与中脑边缘系统多巴胺能机制在建立旨在应对或表明厌恶性质刺激存在的适应性反应中的注意力和认知功能增强一致。CLZ对条件性僵住的选择性作用是由于光/下丘刺激，也可能是由于这种非典型抗精神病药物低剂量产生的已知5-HT(2)受体拮抗作用。
