Research report
Differential involvement of the shell and core subterritories of the nucleus accumbens in latent inhibition and amphetamine-induced activity

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Abstract

Latent inhibition (LI) consists of retardation in conditioning to a stimulus as a consequence of its prior non-reinforced pre-exposure. In view of findings that LI is disrupted in acute schizophrenic patients and evidence from animal experiments pointing to the involvement of the mesolimbic dopamine (DA) system in this phenomenon, the present study investigated the effects of electrolytic lesions to the shell and core subterritories of the nucleus accumbens on LI in rats (Expt. 1). LI was indexed by the amount of suppression of drinking in the presence of a tone that was either pre-exposed or not prior to its pairing with reinforcement (a foot shock). Expt. 2 tested the effects of the DA antagonist, haloperidol, on LI in shell- and core-lesioned animals. Expt. 3 tested the effects of shell and core lesions on spontaneous and amphetamine-induced locomotion. In Expt. 1, LI i.e., lower suppression of drinking in the pre-exposed as compared to the non-pre-exposed animals, was obtained in the sham-operated condition. Core and shell lesions produced distinct effects on LL Animals with core lesions developed LI, but exhibited an overall lower suppression of drinking in comparison to the sham-operated animals. In contrast, shell lesions led to a disappearance of LI. Expt. 2 replicated the differential effects of shell and core lesions on LL although in this experiment, core lesion did not attenuate suppression of drinking. Haloperidol prevented shell-induced abolition of LI In Expt. 3, shell- but not core-lesioned animals were more active than sham controls following amphetamine administration. These results provide evidence for functional differences between the shell and core subregions, as well as for the involvement of the mesolimbic DA system in LI.

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      At the neuronal level, the switching model postulates that ‘CS-no event’ associations are encoded by the entorhinal cortex (EC), causing it to inhibit the nucleus accumbens core (NAcc) which is responsible for initiating the expression of the ‘CS-US’ association. This model is supported by animal studies showing that lesions to the EC disrupt both latent inhibition and learned irrelevance (Allen et al., 2002a; Coutureau et al., 1999; Jeanblanc et al., 2004; Shohamy et al., 2000), while lesions to the NAcc core cause latent inhibition to be abnormally persistent, i.e. the inhibition of CRs is prolonged in lesioned animals as compared to control animals (Gal et al., 2005b; Schiller et al., 2006; Weiner, 2003; Weiner et al., 1996). One limitation of the switching model is that it does not account for how exactly ‘CS-no event’ and ‘CS-US’ associations are acquired and regulated.

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      The nucleus accumbens (NAc) and its connections with the prefrontal cortex, hippocampus, basolateral amygdala area, and entorhinal cortex are thought to play principal roles in the regulation of LI [23]. Especially in the NAc, there are two functionally different sub regions, AcbSh and AcbC, and the lesion of AcbSh disrupts LI while the same treatment of AcbC does not LI [16,18,24]. “Switching models” in LI has been suggested to explain this functional differentiation, in which AcbC facilitates CS-reinforcement contingencies during conditioning while AcbSh suppresses them [23].

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