Effects of the serotonin - receptor antagonist itasetron (DAU 6215) on learning and memory abilities of the rat

Dottorato di ricerca in farmacologia e tossicologia. A.a. 1997-98. Coordinatore Francesco ClementiConsiglio Nazionale delle Ricerche - Biblioteca Centrale - P.le Aldo Moro, 7 Rome; Biblioteca Nazionale Centrale - P.za Cavalleggeri, 1, Florence / CNR - Consiglio Nazionale delle RichercheSIGLEITItal

The Effect of Crocus sativus L. and Its Constituents on Memory: Basic Studies and Clinical Applications

Memory-related disorders are a common public health issue. Memory impairment is frequent in degenerative diseases (such as Alzheimer's disease and Parkinson disease), cerebral injuries, and schizophrenia. The dried stigma of the plant Crocus sativus L. (C. sativus), commonly known as saffron, is used in folk medicine for various purposes. Several lines of evidence suggest that C. sativus and its constituents are implicated in cognition. Here we critically review advances in research of these emerging molecular targets for the treatment of memory disorders, and discuss their advantages over currently used cognitive enhancers as well remaining challenges. Current analysis has shown that C. sativus and its components might be a promising target for cognition impairments

Crocus sativus L. Extract and Its Constituents: Chemistry, Pharmacology and Therapeutic Potential

Natural products or organic compounds isolated from natural sources as primary or secondary metabolites have inspired numerous drugs [...

Crocins, the Bioactive Components of Crocus sativus L., Counteract the Disrupting Effects of Anesthetic Ketamine on Memory in Rats

Consistent experimental evidence suggests that anesthetic doses of the non-competitive N-methyl-d-aspartate (NMDA) receptor antagonist ketamine cause severe memory impairments in rodents. Crocins are among the various bioactive ingredients of the plant Crocus sativus L., and their implication in memory is well-documented. It has not yet been elucidated if crocins are able to attenuate the memory deficits produced by anesthetic ketamine. The present study was undertaken aiming to clarify this issue in the rat. For this aim, the object recognition, the object location and the habituation tests, reflecting non-spatial recognition memory, spatial recognition memory and associative memory, respectively, were utilized. A post-training challenge with crocins (15–30 mg/kg, intraperitoneally (i.p.), acutely) counteracted anesthetic ketamine (100 mg/kg, i.p.)-induced performance impairments in all the above-mentioned behavioral memory paradigms. The current findings suggest that crocins modulate anesthetic ketamine’s amnestic effects

The Nitric Oxide (NO) Donor Sodium Nitroprusside (SNP) and Its Potential for the Schizophrenia Therapy: Lights and Shadows

Schizophrenia is a severe psychiatric disorder affecting up to 1% of the worldwide population. Available therapy presents different limits comprising lack of efficiency in attenuating negative symptoms and cognitive deficits, typical features of schizophrenia and severe side effects. There is pressing requirement, therefore, to develop novel neuroleptics with higher efficacy and safety. Nitric oxide (NO), an intra- and inter-cellular messenger in the brain, appears to be implicated in the pathogenesis of schizophrenia. In particular, underproduction of this gaseous molecule is associated to this mental disease. The latter suggests that increment of nitrergic activity might be of utility for the medication of schizophrenia. Based on the above, molecules able to enhance NO production, as are NO donors, might represent a class of compounds candidates. Sodium nitroprusside (SNP) is a NO donor and is proposed as a promising novel compound for the treatment of schizophrenia. In the present review, we intended to critically assess advances in research of SNP for the therapy of schizophrenia and discuss its potential superiority over currently used neuroleptics

The Nitric Oxide (NO) Donor Molsidomine Counteract Social Withdrawal and Cognition Deficits Induced by Blockade of the NMDA Receptor in the Rat

The deficiency of the gaseous molecule nitric oxide (NO) seems to be critically involved in the pathogenesis of schizophrenia. Thus, molecules that can normalize NO levels, as are NO donors, might be of utility for the medication of this psychiatric disease. The aim of the present study was to detect the ability of the NO donor molsidomine to reduce schizophrenia-like impairments produced by the blockade of the N-methyl-D-aspartate (NMDA) receptor in rats. Molsidomine’s ability to attenuate social withdrawal and spatial recognition memory deficits induced by the NMDA receptor antagonist ketamine were assessed using the social interaction and the object location test, respectively. Further, the efficacy of the combination of sub-effective doses of molsidomine with sub-effective doses of the atypical antipsychotic clozapine in alleviating non-spatial recognition memory deficits was evaluated utilizing the object recognition task. Molsidomine (2 and 4 mg/kg) attenuated social withdrawal and spatial recognition memory deficits induced by ketamine. Co-administration of inactive doses of molsidomine (1 mg/kg) and clozapine (0.1 mg/kg) counteracted delay-dependent and ketamine-induced non-spatial recognition memory deficits. The current findings suggest that molsidomine is sensitive to glutamate hypofunction since it attenuated behavioral impairments in animal models mimicking the negative symptoms and cognitive deficits of schizophrenia. Additionally, the present results support the potential of molsidomine as an adjunctive drug for the therapy of schizophrenia

The metabotropic glutamate 2/3 receptor agonist LY379268 induces anxiety-like behavior at the highest dose tested in two rat models of anxiety

The activation of Group If metabotropic glutamate 2/3 (mGlu(2/3)) receptors reduces the excessive glutamate release that is hypothesized to be associated with neurodegenerative and psychiatric disorders. LY379268 is a highly potent mGlu(2/3) receptor agonist that has shown efficacy in several animal models of stroke, epilepsy, drug abuse, schizophrenia, and pain. The present study investigated the effects of LY379268 on anxiety-like behavior in rats assessed in the light/dark and open held tests. The effects of LY379268 on motility in a locomotor activity chamber were also investigated in rats. Administration of the two lower doses of LY379268 used (0.3 and 1 mg/kg) did not influence rats' performance either in the light/dark or in the open held Lest. Importantly, the administration of a higher LY379268 dose (3 mg/kg) induced decrease in the number of transitions between the light and dark chambers and time spent in the light chamber compared to the vehicle-treated animals in the light/dark Lest. In the open held test, rats that received 3 mg/kg LY379268 made fewer entries and spent less time in the central zone of the apparatus, exhibited a decrease of rearing episodes, but displayed higher grooming activity compared to controls. Nevertheless, the 3 mg/kg dose did not alter locomotor activity compared with vehicle-treated rats in a motility Lest. The present results indicate that the highest LY379268 dose used in this study induced an anxiety-like effect in the light/dark and open held tests that cannot be attributed to changes in locomotor activity, while lower doses had no effect. (C) 2013 Elsevier B.V. All rights reserved

Constituents of Saffron (Crocus sativus L.) as Potential Candidates for the Treatment of Anxiety Disorders and Schizophrenia

Anxiety disorders and schizophrenia are common public health issues. The dried stigma of the plant Crocus sativus L., (C. sativus) commonly known as saffron are used in folk medicine for various purposes. Several lines of evidence suggest that C. sativus, crocins and safranal are implicated in anxiety and schizophrenia. Here, I intend to critically review advances in research of these emerging molecules for the treatment of anxiety and schizophrenia, discuss their advantages over currently used anxiolytics and neuroleptics, as well remaining challenges. Current analysis shows that C. sativus and its components might be a promising class of compounds for the treatment of the above mentioned psychiatric diseases