Differential effects of the CCKA receptor ligands PD-140, 548 and A-71623 on latent inhibition in the rat.

Latent inhibition (LI) is a behavioural paradigm in which repeated exposure to a stimulus without consequence inhibits the formation of any new associations with that stimulus. To the extent that LI reflects a process of learning to ignore irrelevant stimuli, disrupted LI has been suggested as an animal model for the attentional deficits observed in schizophrenia. The antipsychotic potential of cholecystokinin (CCK) stems from its colocalization with dopamine (DA) in the mesolimbic pathway, where it demonstrates both excitatory and inhibitory effects on dopaminergic activity. This may be explained by mediation through different receptor subtypes. A variety of hypotheses has emerged regarding the potential clinical application of subtype-selective CCK-based drugs. The present experiments examined the effects on LI of two selective CCKA ligands: PD-140,548 (a CCKA antagonist, Experiment 1: 0.001, 0.01, and 0.1 mg/kg) and A-71623 (a CCKA agonist, Experiment 2: 0.02, 0.05, and 0.1 mg/kg). In both experiments, the effects of haloperidol (0.1 mg/kg) were also investigated. Animals receiving 0.1 mg/kg of haloperidol or 0.001 or 0.1 mg/kg (but not 0.01 mg/kg) of PD-140,548 treated the preexposed stimulus as irrelevant after a low number of preexposures. In contrast, no facilitatory effect on LI was detectable at any of the A-71623 doses. The finding that A-71623 failed to enhance LI indicates that it is unlikely that this compound would have any antipsychotic effect within the clinical setting. Considering the facilitatory effect exerted by PD-140,548 on LI, it is probable that the inhibition of CCK activity might prove a more promising strategy for the pharmacological treatment of schizophrenia.

Effects of amisulpride, risperidone and chlorpromazine on auditory and visual latent inhibition, prepulse inhibition, executive function and eye movements in healthy volunteers.

In view of the evidence that cognitive deficits in schizophrenia are critically important for long-term outcome, it is essential to establish the effects that the various antipsychotic compounds have on cognition, particularly second-generation drugs. This parallel group, placebo-controlled study aimed to compare the effects in healthy volunteers (n = 128) of acute doses of the atypical antipsychotics amisulpride (300 mg) and risperidone (3 mg) to those of chlorpromazine (100 mg) on tests thought relevant to the schizophrenic process: auditory and visual latent inhibition, prepulse inhibition of the acoustic startle response, executive function and eye movements. The drugs tested were not found to affect auditory latent inhibition, prepulse inhibition or executive functioning as measured by the Cambridge Neuropsychological Test Battery and the FAS test of verbal fluency. However, risperidone disrupted and amisulpride showed a trend to disrupt visual latent inhibition. Although amisulpride did not affect eye movements, both risperidone and chlorpromazine decreased peak saccadic velocity and increased antisaccade error rates, which, in the risperidone group, correlated with drug-induced akathisia. It was concluded that single doses of these drugs appear to have little effect on cognition, but may affect eye movement parameters in accordance with the amount of sedation and akathisia they produce. The effect risperidone had on latent inhibition is likely to relate to its serotonergic properties. Furthermore, as the trend for disrupted visual latent inhibition following amisulpride was similar in nature to that which would be expected with amphetamine, it was concluded that its behaviour in this model is consistent with its preferential presynaptic dopamine antagonistic activity in low dose and its efficacy in the negative symptoms of schizophrenia.

The validity of a latent class typology of adolescent drinking patterns

Objectives: This study examined the validity of a latent class typology of adolescent drinking based on four alcohol dimensions; frequency of drinking, quantity consumed, frequency of binge drinking and the number of alcohol related problems encountered. Method: Data used were from the 1970 British Cohort Study sixteen-year-old follow-up. Partial or complete responses to the selected alcohol measures were provided by 6,516 cohort members. The data were collected via a series of postal questionnaires. Results: A five class LCA typology was constructed. Around 12% of the sample were classified as �hazardous drinkers� reporting frequent drinking, high levels of alcohol consumed, frequent binge drinking and multiple alcohol related problems. Multinomial logistic regression, with multiple imputation for missing data, was used to assess the covariates of adolescent drinking patterns. Hazardous drinking was associated with being white, being male, having heavy drinking parents (in particular fathers), smoking, illicit drug use, and minor and violent offending behaviour. Non-significant associations were found between drinking patterns and general mental health and attention deficient disorder. Conclusion: The latent class typology exhibited concurrent validity in terms of its ability to distinguish respondents across a number of alcohol and non-alcohol indicators. Notwithstanding a number of limitations, latent class analysis offers an alternative data reduction method for the construction of drinking typologies that addresses known weaknesses inherent in more tradition classification methods.

Analysis of Latent Tracks for MeV protons in CR-39

For protons of energy up to a few MeV, the temporal evolution of etched latent tracks in CR-39 nuclear track detector has been numerically modeled by assuming that the electronic energy loss of the protons governs the latent track formation. The technique is applied in order to obtain the energy spectrum of high intensity laser driven proton beams, with high accuracy. The precise measurement of the track length and areal track density have been achieved by scanning short etched, highly populated CR-39 employing atomic force microscope.

Novel linkage to chromosome 20p using latent classes of psychotic illness in 270 Irish high-density families

Background: Several lines of evidence suggest that the clinical heterogeneity of schizophrenia is due to genetic heterogeneity. Genetic heterogeneity may decrease the signal-to-noise ratio in linkage and association studies. Therefore, linkage studies of clinically homogeneous classes of psychotic illness may result in greater power to detect at least some loci.

Enhanced approach for latent semantic indexing using wavelet transform

Latent semantic indexing (LSI) is a technique used for intelligent information retrieval (IR). It can be used as an alternative to traditional keyword matching IR and is attractive in this respect because of its ability to overcome problems with synonymy and polysemy. This study investigates various aspects of LSI: the effect of the Haar wavelet transform (HWT) as a preprocessing step for the singular value decomposition (SVD) in the key stage of the LSI process; and the effect of different threshold types in the HWT on the search results. The developed method allows the visualisation and processing of the term document matrix, generated in the LSI process, using HWT. The results have shown that precision can be increased by applying the HWT as a preprocessing step, with better results for hard thresholding than soft thresholding, whereas standard SVD-based LSI remains the most effective way of searching in terms of recall value.