No abstract

Extinction-induced attenuation of single-phase and two-phase blocking was examined with rats in a conditioned lick-suppression task. In Experiment 1, which compared the effectiveness of single-and two-phase blocking, it was found that single-phase blocking was facilitated by the initiation of training with an A-US trial rather than an AX-UStrial. Single-phase (but not two-phase) blocking was attenuated as a result of 200 extinction trials with the blocking stimulus (Experiment 2). Experiment 3 revealed recovery from two-phase blocking after 800 extinction trials with the blocking stimulus. Recovery from both types of blocking was specific to the blocked CS trained in compound with the extinguished stimulus (Experiment 4). This is the first article to report that the blocking deficit can be reversed by extinguishing the blocking stimulus. These results are discussed in light of acquisition models (i.e., retrospective revaluation) and expression models (i.e., the comparator hypothesis).Kamin (1968) reported reduced conditioned responding to a cue (X) that was paired with an unconditioned stimulus (US) in the presence ofa second cue (A) as a result of A's having been previously paired with the US. This phenomenon, called "blocking," has been traditionally interpreted as an acquisition failure, in which the prior training with A prevents X from acquiring appreciable associative strength during training (e.g., Kamin, 1968;Mackintosh, 1975;Pearce, 1987;Pearce & Hall, 1980;Rescorla & Wagner, 1972). According to acquisitiondeficit models, the blocked stimulus is prevented from forming a strong association with the US; thus, because the subject has presumably not acquired the critical CS-US association, blocking should be irreversible in the absence of further training with the blocked stimulus.However, evidence for an expression-failure (e.g., retrieval-failure) interpretation ofcue-competition effects (of which blocking is one example) has appeared over the last 15 years. Most reports supporting an expressiondeficit view demonstrate reversal of cue-competition effects in the absence offurther training with the target con-

In 4 conditioned lick suppression experiments with rats, the combined effects of latent inhibition treatment followed by overshadowing treatment were assessed as a test of the comparator hypothesis's (R.R. Miller & L.D. Matzel, 1988) explanations of overshadowing and latent inhibition. Experiments 1 and 2 confirmed the prediction of the comparator hypothesis that combined latent inhibition and overshadowing treatments attenuate the response deficit produced by either treatment alone. Furthermore, consistent with the comparator hypothesis, posttraining changes in the associative status of the putative comparator stimulus altered responding to the target conditioned stimulus (Experiment 3), and switching contexts between latent inhibition and overshadowing treatments (Experiment 4) eliminated the interaction between the latent inhibition and overshadowing treatments.

Treatments that attenuate latent inhibition (U) were examined using conditioned suppression in rats. In Experiment 1, retarded conditioned responding was produced by nonreinforced exposure to the CS prior to the CS-US pairings used to assess retardation (Le., conventional U). In Experiment la, retarded conditioned responding was induced by preexposure to pairings of the CS and a weak US prior to retardation-test pairings of the CS with a strong US (Le., Hall-Pearce [1979] U). Both types of U were attenuated by extensive exposure to the training context (Le., context extinction) following the CS-US pairings of the retardation test. Experiment 2 examined the specificity of the attenuated U effect observed in Experiment 1. After preexposure to two different CSs in two different contexts, each CS was paired with a US in its respective preexposure context. One of the two contexts was then extinguished. This attenuated U to a greater degree for the CS that had been trained in the extinguished context. Experiment 3 differentiated the roles in 11 of CS-context associations and context-US associations. Following preexposure to the CS in the training context, U was reduced by further exposure to the CS outside the training context. This observation was interpreted as implicating the CS-context association as a factor in U. Thus, the results of these experiments suggest that U is a performance deficit mediated by unusually strong CS-context associations. Implications for Wagner's (1981) SOP model andMatzel's (1988) comparator hypothesis are discussed.Latent inhibition (Ll), also known as the CS-preexposure effect, is a deficit in Pavlovian responding to a reinforced conditioned stimulus (CS) observed when subjects are exposed to nonreinforced presentations of that CS prior to reinforced training (e.g., Lubow, 1973). Numerous theoretical explanations ofLl have been proposed, almost all of which have presumed that Ll results from a failure by subjects to acquire the CS-unconditionedstimulus (US) association (see, e.g., Lubow, Schnur, 8? Rifkin, 1976;Mackintosh, 1975;Pearce & Hall, 1980;Wagner, 1981). Typically, these theories propose that the nonreinforced pretraining exposure to the target CS decreases attentional or memorial processing of the CS, which impairs the subject's ability to associate the CS with a US when these elements are later paired.However, theories explaining Ll as solely the result of impaired acquisition have been challenged by recent findings which indicate that responding to the CS can be increased by various treatments administered after the retardation-test CS-US pairings. These include a "reminder treatment," which consists of the US administered alone outside the training context (Kasprow, Catterson, Schachtman, & Miller, 1984), and testing that is extensively delayed after the CS-US pairings (Kraemer, Randall, & Carbary, 1991). These observations suggest that CS preexposure produces a reversible performance failure, whereby subjects are slow to respond in accord with the novel contingency encount...

An acute unilateral vestibular lesion leads to a vestibular tone imbalance with nystagmus, head roll tilt and postural imbalance. These deficits gradually decrease over days to weeks due to central vestibular compensation (VC). This study investigated the effects of i.v. N-acetyl-DL-leucine, N-acetyl-L-leucine and N-acetyl-D-leucine on VC using behavioural testing and serial [18F]-Fluoro-desoxyglucose ([18F]-FDG)-μPET in a rat model of unilateral chemical labyrinthectomy (UL). Vestibular behavioural testing included measurements of nystagmus, head roll tilt and postural imbalance as well as sequential whole-brain [18F]-FDG-μPET was done before and on days 1,3,7 and 15 after UL. A significant reduction of postural imbalance scores was identified on day 7 in the N-acetyl-DL-leucine (p < 0.03) and the N-acetyl-L-leucine groups (p < 0.01), compared to the sham treatment group, but not in the N-acetyl-D-leucine group (comparison for applied dose of 24 mg i.v. per rat, equivalent to 60 mg/kg body weight, in each group). The course of postural compensation in the DL- and L-group was accelerated by about 6 days relative to controls. The effect of N-acetyl-L-leucine on postural compensation depended on the dose: in contrast to 60 mg/kg, doses of 15 mg/kg and 3.75 mg/kg had no significant effect. N-acetyl-L-leucine did not change the compensation of nystagmus or head roll tilt at any dose. Measurements of the regional cerebral glucose metabolism (rCGM) by means of μPET revealed that only N-acetyl-L-leucine but not N-acetyl-D-leucine caused a significant increase of rCGM in the vestibulocerebellum and a decrease in the posterolateral thalamus and subthalamic region on days 3 and 7. A similar pattern was found when comparing the effect of N-acetyl-L-leucine on rCGM in an UL-group and a sham UL-group without vestibular damage. In conclusion, N-acetyl-L-leucine improves compensation of postural symptoms after UL in a dose-dependent and specific manner, most likely by activating the vestibulocerebellum and deactivating the posterolateral thalamus.

Unilateral inner ear damage is followed by a rapid behavioural recovery due to central vestibular compensation. In this study, we utilized serial [(18)F]Fluoro-deoxyglucose ([(18)F]FDG)-µPET imaging in the rat to visualize changes in brain glucose metabolism during behavioural recovery after surgical and chemical unilateral labyrinthectomy, to determine the extent and time-course of the involvement of different brain regions in vestibular compensation and test previously described hypotheses of underlying mechanisms. Systematic patterns of relative changes of glucose metabolism (rCGM) were observed during vestibular compensation. A significant asymmetry of rCGM appeared in the vestibular nuclei, vestibulocerebellum, thalamus, multisensory vestibular cortex, hippocampus and amygdala in the acute phase of vestibular imbalance (4 h). This was followed by early vestibular compensation over 1-2 days where rCGM re-balanced between the vestibular nuclei, thalami and temporoparietal cortices and bilateral rCGM increase appeared in the hippocampus and amygdala. Subsequently over 2-7 days, rCGM increased in the ipsilesional spinal trigeminal nucleus and later (7-9 days) rCGM increased in the vestibulocerebellum bilaterally and the hypothalamus and persisted in the hippocampus. These systematic dynamic rCGM patterns during vestibular compensation, were confirmed in a second rat model of chemical unilateral labyrinthectomy by serial [(18)F]FDG-µPET. These findings show that deafferentation-induced plasticity after unilateral labyrinthectomy involves early mechanisms of re-balancing predominantly in the brainstem vestibular nuclei but also in thalamo-cortical and limbic areas, and indicate the contribution of spinocerebellar sensory inputs and vestibulocerebellar adaptation at the later stages of behavioural recovery.

[F]FDG-PET is applicable for serial in vivo monitoring of the TAC mouse model. Myocardial hypertrophy, the dilation of the left ventricle, and the decrease in LVEF could be reliably quantified over time, as well as the developing localized scar. The increase in volume over time is predictive of a high fibrosis load.

Differences in processing representations of conditioned and unconditioned stimuli (CSs and USs) may result from either their temporal order in training (i.e., CSs precede USs) or the greater biological significance of USs. The CS- and US-preexposure effects were used to probe this question. These effects are similar except that context extinction between preexposure and training more readily attenuates the US- than the CS-preexposure effect. In Experiments 1, 2, and 5, context extinction following preexposure to the stimulus that later served as Event 1 in Event 1-->Event 2 pairings alleviated the response deficit due to Event 1 preexposure if Event 1 was biologically significant. In Experiments 3 and 4, context extinction alleviated the response deficit due to Event 2 preexposure if Event 2 was biologically significant. Thus, biological significance and not temporal order determines how a representation will be processed.