Phencyclidine-induced cognitive deficits in mice are improved by subsequent subchronic administration of the antipsychotic drug perospirone: Role of serotonin 5-HT1A receptors

Accumulating evidence suggests that the serotonin 5-HT_1A receptor may play a role in the pathophysiology of schizophrenia. The present study was undertaken to examine the effects of perospirone, an atypical antipsychotic drug with 5-HT_1A receptor agonism, on cognitive deficits in mice after repeated administration of the NMDA receptor antagonist phencyclidine (PCP). Subsequent subchronic (14 days) administration of perospirone (1.0, 3.0, or 10 mg/kg) significantly attenuated PCP (10 mg/kg)-induced cognitive deficits in mice, in a dose-dependent manner. The effects of perospirone (10 mg/kg) were significantly antagonized by co-administration of the selective 5-HT_1A receptor antagonist WAY100635 (1.0 mg/kg). Furthermore, hypothermia by the 5-HT_1A receptor agonist 8-OH DPAT (0.25 mg/kg) was significantly attenuated in mice treated with PCP. Moreover, a receptor binding assay using [³H]WAY100635 revealed that levels of 5-HT_1A receptors in the hippocampus, but not in the frontal cortex, of PCP-treated mice were significantly lower than those of saline-treated mice. These findings suggest that repeated PCP administration alters 5-HT_1A receptor function in the mouse brain, and that subsequent subchronic administration of perospirone ameliorates PCP-induced cognitive deficits via 5-HT_1A receptors. Therefore, perospirone could be a potential therapy for the cognitive deficits observed in schizophrenic patients.     

Anti-carbonic anhydrase II antibody in autoimmune pancreatitis and tubulointerstitial nephritis

Nephrol Dial Transplant 2007; 22: 1273–1275;     

Paradoxical modulation of tendon tap reflex during voluntary contraction in Parkinson's disease.

OBJECTIVE: Inadequate supraspinal modulation of spinal motor control mechanisms such as alpha-gamma coactivation is supposed to cause difficulty in maintaining proper voluntary contraction in Parkinson's disease (PD). METHODS: Subjects were 42 patients with PD and 20 normal volunteers. Soleus H-reflex and tendon tap reflex (T-reflex) were recorded. The maximal reflexes (H(max) and T(max)) at rest were recorded first. Next, the stimulus intensities were fixed to obtain a reflex size of around 25% of M(max) at rest for both H- and T-reflexes, and the reflexes were recorded at rest, during tonic plantarflexion (TPF), and at the onset of plantarflexion. RESULTS: H(max) at rest was 55% and T(max) 30% in normal subjects, while they were 36 and 31%, respectively, in PD. The size ratio of T(max) and H(max) at rest in PD was larger than normal. In PD, the size of H-reflex increased with TPF as in normal subjects, but T-reflex decreased. These changes in T-reflex were correlated with the grade of rigidity, bradykinesia, and time for 10 m gait. H-reflex had no such correlations. CONCLUSIONS: T-reflex was abnormally modulated in PD especially during tonic contraction. SIGNIFICANCE: Inappropriate supraspinal modulation of the spinal reflex pathways disturbs motor performance in PD.     

Inhibitory effects of salmon calcitonin on the tail-biting and scratching behavior induced by substance P and three excitatory amino acids

Summary We have examined the effects of salmon calcitonin (SCT), injected into the cerebral ventricle (i.c.v.), on the tail-biting and scratching behavior induced by the intrathecal injection of different types of nociceptive agents, i.e., substance P, N-methyl-D-aspartate (NMDA), kainate (KA), and quisqualate (Quis). Tail-biting and scratching behavior induced by the 4 substances was significantly inhibited by SCT (i.c.v.) in the same manner: the dose-response curves were U-shaped, and the most effective dose was O.lIU/mouse in all cases. SCT did not, however, completely inhibit tail-biting and scratching behavior. At its most effective dose, the percent inhibition of substance P-, NMDA-, KA- and Quis-induced behavior were 77.9%, 40.2%, 49.4%, and 52.9%, respectively. These results suggest that SCT has the inhibitory effects of substance P- and glutamate receptor agonists-induced nociceptive response in vivo.