Abstracts Prepulse inhibition (PPI) of startle is an operational measure of sensorimotor gating that is often impaired in patients with schizophrenia. Despite the large number of studies, there is considerable variation in PPI outcomes reported. We conducted a systematic review and meta-analysis investigating PPI impairment in patients with schizophrenia compared with healthy control subjects, and examined possible explanations for the variation in results between studies. Major databases were screened for observational studies comparing healthy subjects and patients with schizophrenia for the prepulse and pulse intervals of 60 and 120 ms as primary outcomes, ie, PPI-60 and PPI-120. Standardized mean difference (SMD) and 95% confidence intervals (CI) were extracted and pooled using random effects models. We then estimated the mean effect size of these measures with random effects meta-analyses and evaluated potential PPI heterogeneity moderators, using sensitivity analysis and meta-regressions. Sixty-seven primary studies were identified, with 3685 healthy and 4290 patients with schizophrenia. The schizophrenia group showed reduction in sensorimotor gating for both PPI-60 (SMD = −0.50, 95% CI = [−0.61, −0.39]) and PPI-120 (SMD = −0.44, 95% CI = [−0.54, −0.33]). The sensitivity and meta-regression analysis showed that sample size, gender proportion, imbalance for gender, source of control group, and study continent were sources of heterogeneity (P < .05) for both PPI-60 and PPI-120 outcomes. Our findings confirm a global sensorimotor gating deficit in schizophrenia patients, with overall moderate effect size for PPI-60 and PPI-120. Methodological consistency should decrease the high level of heterogeneity of PPI results between studies.

Schizophrenic patients show deficits on stimulus salience tasks such as latent inhibition and blocking, which measure the ability to disregard irrelevant stimuli. Amphetamine-treated animals show similar deficits in analogous tasks, thereby providing a model of the stimulus-selection deficits observed in schizophrenia. In two experiments, the effect of the indirect dopamine (DA) agonist D-amphetamine sulphate (1.0 mg/kg, i.p.) on Kamin blocking and overshadowing were examined and compared, in the rat, using the conditioned lick suppression procedure. The aim was to provide some insight into the behavioural and pharmacological mechanisms underlying amphetamine effects in both paradigms. In experiment 1, it was shown that amphetamine selectively disrupted Kamin blocking, when given either at stage 2 alone, or at both stages of the task. In experiment 2, amphetamine treatment significantly abolished Kamin blocking and overshadowing, when administered prior to compound conditioning in both tasks. These data suggest that dopamine may play a critical role in mediating performance in tasks measuring stimulus salience processes. The results are discussed in the framework of the role of DA in stimulus-selection performance.

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l‐DOPA is still the drug of choice to treat Parkinson’s disease although adverse side effects appear after several years of treatment. These are thought to be the consequence of plastic re‐arrangements of the nigrostriatal connections, such as sprouting of the dopaminergic terminals or post‐synaptic changes. Pleiotrophin, a trophic factor that we have shown to be up‐regulated in the striatum of parkinsonian rats after long‐term l‐DOPA treatment may play a role in these plastic changes. To determine whether one of the three known pleiotrophin receptors [N‐syndecan, receptor protein tyrosine phosphatase type zeta beta (RPTP‐ζ/β) and anaplastic lymphoma kinase] might be implicated in these putative plastic effects, we quantified their expression levels by real‐time RT‐PCR in the striatum and mesencephalon of rats with partial lesions of the nigrostriatal pathway undergoing l‐DOPA treatment. Both pleiotrophin and RPTP‐ζ/β expression was up‐regulated in the striatum but not in the mesencephalon of lesioned rats and RPTP‐ζ/β expression was even further increased by l‐DOPA. The levels of the RPTP‐ζ/β protein were also increased in the striatum of l‐DOPA‐treated lesioned rats. Immunofluorescence labeling showed the protein to be constitutively expressed in striatal medium spiny neurons, which are innervated by both the corticostriatal glutamatergic and nigrostriatal dopaminergic systems. RPTP‐ζ/β might therefore be implicated in the plastic changes triggered by l‐DOPA treatment and might merit further study as a potential candidate for Parkinon’s disease therapy.