Disruption of latent inhibition in ISIAH rats with stress-sensitive arterial hypertension

Latent inhibition phenomenon is used in the study of processes of selective attention in the context reinforcing training. The purpose of this study was a comparative analysis of the ability to ignore irrelevant stimuli in hypertensive ISIAH rats and normotensive Wistar rats with different psychoemotional statuses. Latent inhibition was formed in the passive and active avoidance tasks the development of which was preceded by repeated presentation (pre-exposition) conditioned stimulus without reinforcement. In ISIAH rats, disruption of latent inhibition in both behavioural tasks was observed as compared with Wistar rats. These data suggest that the deficit of selection information in ISIAH rats is caused by congenital weakness of internal inhibition in the adaptation to anxiogenic stimuli.     

Toxicity of cholecalciferol to rats in a multi-species bait

The effectiveness of Feracol?, a possum control paste bait containing 0.8% cholecalciferol, as a rodenticide has been assessed in cage and field trials. Caged rats were provided with toxic bait in choice and no-choice tests. Feracol? was readily eaten when presented as the sole food source or with other food, and was effective at killing rats in both situations. Wild-caught and laboratory rats (n =?35), comprising both ship (Rattus rattus) and Norway rats (R.?norvegicus), were presented with 30 g of Feracol? alone or with an equivalent toxic bait over 48 h. Thirty-four rats died in an average of 4.0 days. Having established that the paste, originally designed for possum control, is also an effective rodenticide for rat control, field trials were initiated with the paste delivered in the field in Philproof? and Striker? bait stations. Monitoring of rat numbers before and after application of toxic bait was undertaken at three trial sites, Lions Hut, Mangaone and Pakoakoa, in Te Urewera National Park in the North Island of New?Zealand. Rat population density was assessed using tracking tunnels. Philproof? bait stations containing 200 g of Feracol? were placed 50 m apart on grids at Lions Hut and monitoring was undertaken at one location per hectare using tracking tunnels. At Mangaone and Pakoakoa, two Striker? bait stations containing 18 g of Feracol? were sited at 25-m intervals on lines 150 m apart, and monitoring was undertaken with five lines of 10 tunnels at 50-m intervals. At Lions Hut, rat tracking decreased from 78% to 3% of tunnels tracked; at Mangaone the reduction was 51% to 0%; and at Pakoakoa from 36% to 0%. These trials demonstrate that Feracol? is effective at reducing both moderate and high concentrations of ship rats in the Philproof? and Striker? bait station delivery systems.     

Monoaminoxidase activity and serotonin metabolism in the brain of rats during latent inhibition]

The monoamine oxidase (MAO) activities and the concentrations of 5-HT and 5-hydroxyindoleacetic acid were investigated in four brain regions in rats during the acquisition of latent inhibition in one-trial passive avoidance task. 5-HT metabolism was not altered in the hippocampus. Changes of 5-HT metabolism were found in the frontal cortex during testing of latent inhibition and were accompanied by lowering of MAO activity. No change of 5-HT metabolism was observed in this structure at the stage of pre-exposition to conditioned stimulus. 5-HT metabolism was activated at the stage of pre-exposition to conditioned stimulus in the amygdala and striatum and was maintained on high level, in these structures during testing of latent inhibition. The data presented here indicate that serotoninergic system in various brains regions is specifically involved in the formation of different stages of latent inhibition.     

Impairment of latent inhibition in OXYS rats with hereditary syndrome of premature aging

The effect of latent inhibition has been tested in OXYS (strain selected for accelerated aging) and Wistar (control) rats at the age of 4 months using a conditioned passive avoidance reaction. The OXYS rats displayed a higher level of anxiety in the elevated plus-maze as compared to Wistar strain. The experimental procedure consisted of preexposure stage (presentation of non-reinforced environmental stimulus), conditioning (presentation of a preexposed stimulus paired with shock), and testing the effect of latent inhibition. The effect of latent inhibition was revealed only in Wistar rats, in which the latency of transition to the dark compartment of the experimental chamber was reduced. Contrastingly, in OXYS rats the conditioned performance was not inhibited. It is suggested that aging-associated factors such as the low rate of habituation to experimental situation at the preexposure stage and the high general anxiety level of OXYS rats can interfere with inhibition of the attention to irrelevant information.     

The dynamics of latent inhibition in rats under the action of substance P]

The role of substance P in latent inhibition was studied in experiments on rats. Administration of neuropeptide during pre-exposition of conditioned stimulus and before conditioning disturbed all signs of latent inhibition: level of reproduction, retention and resistance to amnestic action of conditioned reaction in the task of passive avoidance. Single administration of haloperidol before learning prevented the disturbance. Significance of hyperfunction of substance P in selective attention and pathogenesis of schizophrenia is discussed.     

Appetitive latent inhibition in rats: preexposure performance does not predict conditioned performance

Nonreinforced preexposure to a conditioned stimulus impairs subsequent conditioning with that stimulus. The goal of these studies was to assess the extent to which acquisition performance could be predicted from preexposure performance using a correlational approach. For both preexposure and autoshaping, four measures of performance were computed, including overall average lever pressing, lever pressing in the initial session, percentage change in lever pressing, and slopes. These measures were correlated in a large sample of rats trained in an autoshaping situation. None of the three measures of autoshaping performance was consistently predicted by any of the three measures of preexposure performance. These results are consistent with the view that latent inhibition is not reducible to long-term habituation.     

Summation of excitation and inhibition in a second order sensory neuron investigated by computer simulation

Dorsal spinocerebellar tract (DSCT) neurones adequately activated by primary afferents from the muscle spindles in one muscle in the hindleg of the cat, is regularly inhibited by primary afferents from other muscles. The inhibitory input causes a constant reduction in firing frequency independent of the excitatory drive of the cell. In a simple model the effects of presynaptic inhibition and of postsynaptic inhibition with different time course of the inhibitory action, have been explored. Within the scope of this model, only postsynaptic inhibition with a very long time-constant could explain the experimental results. It is suggested that the inhibitory action is transmitted to the DSCT-cell through a number of synapses distributed over the dendrites.     

Chemical ligation--an unusual paradigm in protease inhibition

Some protease inhibitors use uncommon mechanisms to restrain the activity of their target enzymes. A recent paper in Chemistry and Biology (Lu et al., 2006) demonstrates a curious mechanism of inhibition of a caspase, relying on principles of native peptide ligation.     

The interaction of the serotonin and dopaminergic systems of the brain in the mechanisms of latent inhibition in rats

Decrease of serotonin concentration in the septo-hippocampal region of Wistar male rats was obtained by introduction of 5,7-dihydroxytryptamine in the raphe median nucleus. In seven days, after 20 pre-expositions of the conditioned stimulus (presentation of the experimental chamber) conditioned reaction of passive avoidance was elaborated. In sham-operated control the pre-exposition of the conditioned stimulus caused latent inhibition, determined by several parameters: low level of conditioned reaction reproduction, its prolonged preservation at the formed level and nonsubjection to amnesia. Introduction of haloperidol in a dose of 0.5 mg/kg one hour before learning restored the state of latent inhibition disturbed by switching off of the mesolimbic serotonin system. It is supposed that in the state of pre-exposition, the decrease of attention to nonreinforced stimulus takes place because of the intensification of inhibitory influence of the serotoninergic system and reciprocal decrease of dopaminergic system activity.     

Summation of excitation and inhibition in the slowly adapting stretch receptor neuron of the crayfish

The slowly adapting stretch receptor of the crayfish is inhibited via the large accessory neuron both by reflex activation of this inhibitory interneuron from the stretch receptor itself (autogenic inhibition) and by activation of the interneuron from stretch receptors in other abdominal segments (neighbourinhibition). Neighbour-inhibition increases proportionally with the increase in impulse frequency in the large accessory neuron produced by activity in neighbouring receptors and largely independently of the level of excitation in the stretch receptor itself. A simple model based on intracellular recordings from the receptor neuron predicts this behaviour fairly accurately. In this model each receptor impulse is followed by an IPSP after a delay proportional to the uninhibited interspike interval of the receptor (autogenic inhibition). The other IPSP's arrive randomly distributed in time (neighbour-inhibition). An alternative model in which all IPSP's arrive randomly produces similar results. This latter model can be modified to fit other neuronal systems.     

Haloperidol treatment at pre-exposure phase reduces the disturbance of latent inhibition in rats with neonatal ventral hippocampus lesions

Animals with neonatal ventral hippocampal lesions develop during or after adolescence abnormal behaviors related to schizophrenia such as anxiety and latent inhibition disruption. The aim of this study was to test whether haloperidol injection prior to pre-exposure session in the latent inhibition test would facilitate latent inhibition.     

On generalized latent factor modeling and inference for high-dimensional binomial data

We explore a hierarchical generalized latent factor model for discrete and bounded response variables and in particular, binomial responses. Specifically, we develop a novel two-step estimation procedure and the corresponding statistical inference that is computationally efficient and scalable for the high dimension in terms of both the number of subjects and the number of features per subject. We also establish the validity of the estimation procedure, particularly the asymptotic properties of the estimated effect size and the latent structure, as well as the estimated number of latent factors. The results are corroborated by a simulation study and for illustration, the proposed methodology is applied to analyze a dataset in a gene–environment association study.     

Distinctions in metabolism of serotonin and dopamine in rat brain during latent inhibition

Latent inhibition (LI) is a behavioral phenomenon, in which repeated presenting of a non-reinforced stimulus retards conditioning to this stimulus when it is coupled with a reinforcer. In order to find specific serotonin (5-HT- and dopamine (DA) changes mediating the LI, the 5-HT and DA metabolism was investigated in certain brain regions. Oxidative deamination of 5-HT and DA by monoamine oxidase (MAO) was determined in the prefrontal cortex, striatim, amygdala, and hippocampus at preexposure and testing stages of the LI using the passive avoidance procedure in rats. Preexposed animals demonstrated high MAO activity for 5-HT deamination in the amygdala and striatum and lower MAO activity for DA deamination in the amygdala and hippocampus. After testing the LI, a high level of 5-HT deamination by MAO was revealed in the amygdala, white the lower level of 5-HT deamination by MAO was shown in the prefrontal cortex. At the same time, no changes in DA metabolism were found in all the brain regions studied. Thus, the role of dopaminergic system in the LI effect may be limited by the preexposure stage. The obtained evidence suggests that the enhanced 5-HT activity in the amygdala and striatum induced by the preexposed stimulus is a principal biochemical mechanism underlying the LI.     

Epstein-Barr virus provides a new paradigm: a requirement for the immediate inhibition of apoptosis

DNA viruses such as herpesviruses are known to encode homologs of cellular antiapoptotic viral Bcl-2 proteins (vBcl-2s), which protect the virus from apoptosis in its host cell during virus synthesis. Epstein-Barr virus (EBV), a human tumor virus and a prominent member of γ-herpesviruses, infects primary resting B lymphocytes to establish a latent infection and yield proliferating, growth-transformed B cells in vitro. In these cells, 11 viral genes that contribute to cellular transformation are consistently expressed. EBV also encodes two vBcl-2 genes whose roles are unclear. Here we show that the genetic inactivation of both vBcl-2 genes disabled EBV's ability to transform primary resting B lymphocytes. Primary B cells infected with a vBcl-2-negative virus did not enter the cell cycle and died of immediate apoptosis. Apoptosis was abrogated in infected cells in which vBcl-2 genes were maximally expressed within the first 24 h postinfection. During latent infection, however, the expression of vBcl-2 genes became undetectable. Thus, both vBcl-2 homologs are essential for initial cellular transformation but become dispensable once a latent infection is established. Because long-lived, latently infected memory B cells and EBV-associated B-cell lymphomas are derived from EBV-infected proapoptotic germinal center B cells, we conclude that vBcl-2 genes are essential for the initial evasion of apoptosis in cells in vivo in which the virus establishes a latent infection or causes cellular transformation or both.     

Stimulus comparison in perceptual learning: roles of sensory preconditioning and latent inhibition

Rats were given exposure to a compound flavour (AX) and to one element of that compound (X). Two drinking tubes were made available to the rat on each exposure trial. For group concurrent (CNC) one tube contained AX and the other X. For groups alternating (ALT) and blocked (BLK), however, both tubes contained the same flavour (AX or X). Group ALT received AX and X on alternate trials; group BLK received AX in the first block of trials and X on the second, or vice versa. After an aversion had been established to X the groups were tested with AX. It was found that group ALT showed less generalization from X to AX than did group BLK. This difference was not accompanied by a parallel difference in the level of conditioning to X. However, group CNC showed both stronger conditioning to X and greater generalization from X to AX than groups ALT and BLK. Implications for the role of stimulus comparison in the perceptual learning effect are discussed.     

Participation of the central noradrenergic system in the mechanisms of latent inhibition

Male Wistar rats were learnt to conditioned reaction of passive avoidance 10 days after intraperitoneal administration of 50 mg/kg of specific neurotoxin DSP4. The character of conditioned reaction reproduction, duration of its conservation and its stability against amnestic processing were analyzed. It has been found that reduction of activity of noradrenergic coerulo-cortical system does not influence the conditioned reaction reproduction but inhibits its spontaneous extinction and prevents amnesia development. The obtained data are discussed in aspect of central noradrenaline participation in latent inhibition mechanisms.