Evidence for a critical role of entorhinal cortex at pre-exposure for latent inhibition disruption in rats.

Latent inhibition (LI), that is the decrease in conditioned response induced by the repeated nonreinforced pre-exposures to the to-be-conditioned stimulus, is disrupted by entorhinal cortex (EC) lesions. The mechanism involved in this disruption is unknown, and in particular the experimental stage (pre-exposure or conditioning) at which the integrity of EC is necessary has to be determined. The purpose of this study was to address this issue by using reversible inactivation of the EC by local micro-infusion of tetrodotoxin (TTX). TTX was infused either before the pre-exposure phase, before the conditioning phase, or before both phases. LI was unaffected in rats that received TTX before conditioning or before both pre-exposure and conditioning. In contrast, LI was disrupted in rats that received TTX before pre-exposure only. These results are discussed in the framework of LI models.

Systemic or intra-accumbens injection of D-amphetamine delays habituation to a tone stimulus in rats.

Dopamine release within the nucleus accumbens shell is suggested to control the salience of environmental stimuli, and previous research has shown that the indirect dopamine agonist D-amphetamine can alter the salience of both aversive and neutral stimuli. In experiment 1, the effect of systemic injection of D-amphetamine (0.5, 1 mg/kg) on fear conditioning to a tone was assessed in an 'off-baseline' conditioned suppression procedure using several footshock intensities. Although the effects of amphetamine on conditioning were unclear, the results indicated a deficit of simple tone habituation in amphetamine-treated rats. In experiment 2, habituation of the orienting reaction to a tone was assessed by the progressive reduction of lick suppression upon repeated presentation of the auditory stimulus. D-Amphetamine delayed tone habituation, whether administered systemically (0.5, 1 mg/kg) or into the nucleus accumbens shell (3, 10 microg/0.5 microl). These data are consistent with electrophysiological and neurochemical data demonstrating the role of nucleus accumbens dopamine in novelty processing. The relevance of the data to latent inhibition is discussed.