Elsevier

Neuroscience

Volume 75, Issue 2, 25 October 1996, Pages 535-542
Neuroscience

Prepulse inhibition and latent inhibition: the role of dopamine in the medial prefrontal cortex

https://doi.org/10.1016/0306-4522(96)00307-7Get rights and content

Abstract

The prefrontal cortex has often been implicated in the pathophysiology of schizophrenia. Schizophrenic patients are known to suffer from certain information processing deficits, which can be detected, among others, in the prepulse inhibition and the latent inhibition paradigm. The present study was designed to investigate the role of dopamine receptors in the medial prefrontal cortex in prepulse inhibition and latent inhibition. The results show that the local application of the selective antagonist of the dopamine D1-like receptor family, SCH 39166, into the medial prefrontal cortex dose-dependently reduced prepulse inhibition. Likewise, the selective antagonist of the dopamine D2-like receptor family, sulpiride, injected into the medial prefrontal cortex dose-dependently reduced prepulse inhibition. Neither of these antagonists, however, influenced latent inhibition as measured with the conditioned taste aversion paradigm. These data further indicate that the neuronal substrates of latent inhibition and prepulse inhibition are clearly different.

Since the prefrontal cortex is intimately related to subcortical dopamine, the possible differential involvement of subcortical dopaminergic terminal fields in prepulse inhibition and latent inhibition is discussed.

Section snippets

Animals and surgery

Male Wistar rats (bred at the Central Animal Laboratory of the University of Nijmegen), weighing 180–200 g at the time of the operation, were used. Rats were stereotaxically implanted with guide cannulae aimed at the prelimbic part of the prefrontal cortex, under sodium pentobarbital anaesthesia (Narcoved®, 60 mg/kg i.p.). In a recent c-Fos study (Ellenbroek et al., unpublished observations), we have found that especially this part of the prefrontal cortex is involved in prepulse inhibition.

Injection sites

Almost all of the rats had injections situated within the boundaries of the Cingulate Cortex Area 3 as delineated by Paxinos and Watson.[28]The area in which the injections were localized is shown in Fig. 1. The data of rats with injection sites outside this area (n = 2) were discarded from the analysis.

Prepulse inhibition

The local application of dl-sulpiride or SCH 39166 into the medial prefrontal cortex did not affect basal startle reactivity (Fig. 2A) nor habituation (measured as the ratio of the last five over

Discussion

The present results show that blockade of dopamine receptors within the medial prefrontal cortex (especially the prelimbic area or the Cingulate Cortex Area 3 as described by Paxinos and Watson[28]) significantly reduced prepulse inhibition, whereas it had no effect on the degree of latent inhibition as measured with the conditioned taste aversion paradigm. Before discussing the relevance of these data, it is important to realize the possible effects of the stereotaxic operation or the

Conclusion

The present study shows that local application of SCH 39166 (a selective antagonist of the dopamine D1-like receptor family) and of dl-sulpiride (a selective antagonist of the dopamine D2-like receptor family) into the medial prefrontal cortex reduced prepulse inhibition of the acoustic startle response. Neither treatment, however, affected latent inhibition of the conditioned taste aversion paradigm. These results add further support to the hypothesis that these aspects of information

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