Social interaction of rats is related with baseline prepulse inhibition level.

The symptoms of schizophrenia are evaluated in three general categories: positive, negative and cognitivesymptoms. Disruption of prepulse inhibition (PPI) of the acoustic startle reflex is commonly used to modelpositive and cognitive symptoms in experimental animals. On the other hand, deficient social interaction(SI) is a common model of negative symptoms. Here we tested whether PPI provides information aboutnegative symptoms by using a SI test. Baseline PPI and its relation with anxiety-like behavior were alsoexamined with elevated plus maze (EPM) test. In the first experiment, baseline PPI levels of 30 Wistarrats were measured and animals with the highest 1/3 and the lowest 1/3 of PPI scores were respectivelyassigned in high-inhibitory (HI) and low-inhibitory (LI) groups. Subsequently, rats in the HI and LI groupswere paired with animals from the same group and tested for SI. In the second experiment, another batchof animals was assigned to HI and LI groups and they were investigated in the EPM test. The results demon-strate a significant difference between the PPI values of HI and LI groups. Both the SI time and the movingdistance of LI rats were significantly lower, and the average distance between rat pairs was significantlylonger than HI rats. In the EPM test LI and HI rats showed similar levels of anxiety-like behaviors, howeverour results imply that performance of the rats in the SI test is related to baseline PPI levels. Thus PPI testcan provide predictive information about the outcome of animal models for negative symptoms in rats

Varenicline disrupts prepulse inhibition only in high-inhibitory rats.

Varenicline, a widely used smoking cessation drug, has partial agonistic activity at α4β2 nicotinic receptors, and full agonistic activity at α7 nicotinic receptors. Thus it may interact with cognitive processes and may alleviate some of the cognitive disturbances observed in psychotic illnesses such as schizophrenia. We aimed to test the effects of varenicline on sensorimotor gating functioning, which is crucial for normal cognitive processes, especially for the integration of sensory and cognitive information processing and the execution of appropriate motor responses. Prepulse inhibition (PPI) of the acoustic startle reflex was used to test the sensorimotor gating functioning. First, the effects of varenicline and nicotine on rats having high or low baseline PPI levels were evaluated; then, varenicline was applied prior to apomorphine (0.5 mg/kg), and MK-801 (0.15 mg/kg), which are used as comparative models of PPI disruption. Varenicline (0.5–3 mg/kg) did not change PPI when given alone in naïve animals. When rats were selected according to their baseline PPI values, varenicline (1 mg/kg) significantly decreased PPI in high–inhibitory (HI) but not in low–inhibitory (LI) rats. Nicotine (1 mg/kg; tartrate salt) produced a similar activity in LI and HI groups. In combination experiments, varenicline did not reverse either apomorphine or the MK-801-induced disruption of PPI. These results demonstrate that the effects of both varenicline and nicotine on sensorimotor gating are influenced by the baseline PPI levels. Moreover, varenicline has no effect on apomorphine or the MK-801-induced disruption of PPI

Increased plasma agmatine levels in patients with schizophrenia

Agmatine is an endogenous substance, synthesized from L-arginine, and it is proposed to be a new neurotransmitter. Preclinical studies indicated that agmatine may have an important role in the pathophysiology of schizophrenia. This study was organized to investigate plasma agmatine in patients with schizophrenia and in healthy controls. Eighteen patients with schizophrenia and 19 healthy individuals constituted the subjects. Agmatine levels in the plasma were measured using the HPLC method. The S100B protein level, which is a peripheral biomarker for brain damage, was also measured using the ELISA method. While plasma levels of agmatine in patients with schizophrenia were significantly increased (p < 0.0001) compared to those of healthy individuals (control), there were no significant changes in the levels of S100B protein (p ¼ 0.660). An ROC (receiver operating characteristic) curve analysis revealed that measuring plasma agmatine levels as a clinical diagnostic test would significantly differentiate between patients with schizophrenia and those in the control group (predictive value: 0.969; p < 0.0001). The predictive value of S100B measurements was not statistically significant (p > 0.05). A multiple regression analysis revealed that the age of the patient and the severity of the illness, as indicated by the PANSS score, significantly contributed the plasma agmatine levels in patients with schizophrenia. These results support the hypothesis that an excess agmatine release is important in the development of schizophrenia. The findings also imply that the plasma agmatine level may be a potential biomarker of schizophrenia