Melo Liana L, Pereira Ellen C H M, Pagini Cássia H, Coimbra Norberto C, Brandão Marcus L, Ferrari Elenice A M
Laboratório de Neuropsicofarmacologia, Universidade São Francisco, Bragança Paulista, SP, Brazil.
Exp Neurol. 2009 Mar;216(1):16-21. doi: 10.1016/j.expneurol.2008.10.020. Epub 2008 Nov 24.
Electrical or chemical stimulation of the inferior colliculus (IC) induces fear-like behaviors. More recently, consistent evidence has shown that electrical stimulation of the central nucleus of the IC supports Pavlovian conditioning and latent inhibition (LI). LI is characterized by retardation in conditioning and also by an impaired ability to ignore irrelevant stimuli, after a non-reinforced pre-exposure to the conditioned stimulus. LI has been proposed as a behavioral model of cognitive abnormalities seen in schizophrenia. The aim of the present study was to determine whether dopaminergic mechanisms in the IC are involved in LI of the conditioned emotional response (CER). To induce LI, a group of rats was pre-exposed (PE) to six tones in two sessions, while rats that were not pre-exposed (NPE) had two sessions without tone presentations. The conditioning consisted of two tone presentations to the animal, followed immediately by a foot shock. PE and NPE rats received IC microinjections of physiological saline, the dopaminergic agonist apomorphine (9.0 microg/0.5 microL/side), or the dopaminergic antagonist haloperidol (0.5 microg/0.5 microL/side) before both pre-exposure and conditioning. During the test, the PE rats that received saline or haloperidol had a lower suppression of the licking response compared to NPE rats that received vehicle or haloperidol, indicating that latent inhibition was induced. There was no significant difference in the suppression ratio in rats that received apomorphine injections into the IC, indicating reduced latent inhibition. These results suggest that dopamine-mediated mechanisms of the IC are involved in the development of LI.
对下丘(IC)进行电刺激或化学刺激会诱发类似恐惧的行为。最近,有一致的证据表明,对IC中央核进行电刺激可支持巴甫洛夫条件反射和潜伏抑制(LI)。LI的特征在于条件反射延迟,以及在对条件刺激进行非强化预暴露后忽略无关刺激的能力受损。LI已被提出作为精神分裂症中所见认知异常的行为模型。本研究的目的是确定IC中的多巴胺能机制是否参与条件性情绪反应(CER)的LI。为了诱导LI,一组大鼠在两个时段中预先暴露(PE)于六个音调,而未预先暴露(NPE)的大鼠有两个不呈现音调的时段。条件反射包括向动物呈现两个音调,随后立即进行足部电击。在预暴露和条件反射之前,PE和NPE大鼠均接受IC微量注射生理盐水、多巴胺能激动剂阿扑吗啡(9.0微克/0.5微升/侧)或多巴胺能拮抗剂氟哌啶醇(0.5微克/0.5微升/侧)。在测试期间,与接受溶剂或氟哌啶醇的NPE大鼠相比,接受生理盐水或氟哌啶醇的PE大鼠舔舐反应的抑制程度较低,表明诱导了潜伏抑制。向IC注射阿扑吗啡的大鼠的抑制率没有显著差异,表明潜伏抑制降低。这些结果表明,IC中多巴胺介导的机制参与了LI的发展。