The contextual fear conditioning deficit presented by spontaneously hypertensive rats (SHR) is not improved by mood stabilizers

Objectives: We have recently reported that spontaneously hypertensive rats (SHR) present a contextual fear conditioning (CFC) deficit. This deficit is improved by antipsychotic drugs, potentiated by proschizophrenia manipulations and not altered by acute administration of carbamazepine, lamotrigine and valproic acid. Nevertheless, the effects of lithium a classical mood stabilizer or repeated treatment with these drugs were not evaluated. the main aim of the present study was to extend our previous work by investigating a possible beneficial effect of acute and/or chronic treatments with lithium or lamotrigine on the acquisition deficit of CFC presented by SHR.Methods: Rats were submitted to CFC task after an acute treatment with lithium and/or a repeated treatment with lithium and lamotrigine.Results: Our data revealed that the CFC deficit presented by SHR is not improved by acute or repeated treatment with lithium. Repeated lamotrigine treatment potentiated the deficit presented by SHR and impaired CFC in control animals (Wistar Rats).Conclusions: These data reinforce the absence of beneficial effects of mood stabilizers on the emotional context processing impairment modeled by SHR. (C) 2011 Elsevier Inc. All rights reserved.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Universidade Federal de São Paulo, Dept Psychiat, LiNC, BR-04039032 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Pharmacol, BR-04039032 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Psychiat, LiNC, BR-04039032 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Pharmacol, BR-04039032 São Paulo, BrazilWeb of Scienc

Effects of cannabinoid drugs on the deficit of prepulse inhibition of startle in an animal model of schizophrenia: the SHR strain

Clinical and neurobiological findings suggest that the cannabinoids and the endocannabinoid system may be implicated in the pathophysiology and treatment of schizophrenia. We described that the spontaneously hypertensive rats (SHR) strain presents a schizophrenia behavioral phenotype that is specifically attenuated by antipsychotic drugs, and potentiated by proschizophrenia manipulations. Based on these findings, we have suggested this strain as an animal model of schizophrenia. the aim of this study was to evaluate the effects of cannabinoid drugs on the deficit of prepulse inhibition (PPI) of startle, the main paradigm used to study sensorimotor gating impairment related to schizophrenia, presented by the SHR strain. the following drugs were used: (1) WIN55212,2 (cannabinoid agonist), (2) rimonabant (CB1 antagonist), (3) AM404 (anandamide uptake inhibitor), and (4) cannabidiol (CBD; indirect CB1/CB2 receptor antagonist, among other effects). VVistar rats (VVRs) and SHRs were treated with vehicle (VEH) or different doses of WIN55212 (0.3, 1, or 3 mg/kg), rimonabant (0.75, 1.5, or 3 mg/kg), AM404 (1, 5, or 10 mg/kg), or CBD (15, 30, or 60 mg/kg). VEH-treated SHRs showed a decreased PPI when compared to VVRs. This PPI deficit was reversed by 1 mg/kg WIN and 30 mg/kg CBD. Conversely, 0.75 mg/kg rimonabant decreased PPI in SHR strain, whereas AM404 did not modify it. Our results reinforce the role of the endocannabinoid system in the sensorimotor gating impairment related to schizophrenia, and point to cannabinoid drugs as potential therapeutic strategies.Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Universidade Federal de São Paulo, Dept Pharmacol, BR-04039032 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Psychiat, Lab Interdisciplinar Neurociencias Clin, BR-04039032 São Paulo, BrazilUniv São Paulo, Dept Neurosci & Behav, BR-14049 Ribeirao Preto, BrazilNatl Council Sci & Technol Dev, Natl Inst Sci & Technol Translat Med, Ribeirao Preto, BrazilUniversidade Federal de São Paulo, Dept Pharmacol, BR-04039032 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Psychiat, Lab Interdisciplinar Neurociencias Clin, BR-04039032 São Paulo, BrazilFAPESP: FAPESP - 2010/07994-3Web of Scienc

Cannabidiol Prevents Motor and Cognitive Impairments Induced by Reserpine in Rats

Cannabidiol (CBD) is a non-psychotomimetic compound from Cannabis sativa that presents antipsychotic, anxiolytic, anti-inflammatory, and neuroprotective effects. In Parkinson's disease patients, CBD is able to attenuate the psychotic symptoms induced by L-DOPA and to improve quality of life. Repeated administration of reserpine in rodents induces motor impairments that are accompanied by cognitive deficits, and has been applied to model both tardive dyskinesia and Parkinson's disease. The present study investigated whether CBD administration would attenuate reserpine-induced motor and cognitive impairments in rats. Male Wistar rats received four injections of CBD (0.5 or 5 mg/kg) or vehicle (days 2-5). On days 3 and 5, animals received also one injection of 1 mg/kg reserpine or vehicle. Locomotor activity, vacuous chewing movements, and catalepsy were assessed from day 1 to day 7. On days 8 and 9, we evaluated animals' performance on the plus-maze discriminative avoidance task, for learning/memory assessment. CBD (0.5 and 5 mg/kg) attenuated the increase in catalepsy behavior and in oral movements - but not the decrease in locomotion induced by reserpine. CBD (0.5 mg/kg) also ameliorated the reserpine-induced memory deficit in the discriminative avoidance task. Our data show that CBD is able to attenuate motor and cognitive impairments induced by reserpine, suggesting the use of this compound in the pharmacotherapy of Parkinson's disease and tardive dyskinesia.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Univ Fed Sao Paulo, Dept Psychiat, Interdisciplinary Lab Clin Neurosci, Sao Paulo, BrazilUniv Fed Sao Paulo, Dept Pharmacol, Sao Paulo, BrazilUniv Fed Sao Paulo, Dept Psychobiol, Sao Paulo, BrazilUniv Sao Paulo, Dept Neurosci & Behav, Ribeirao Preto, BrazilNatl Council Sci & Technol Dev, Natl Inst Translat Med, Ribeirao Preto, BrazilInterdisciplinary Laboratory of Clinical Neurosciences, Department of Psychiatry, Universidade Federal de São Paulo (UNIFESP), São Paulo, BrazilDepartment of Pharmacology, Universidade Federal de São Paulo (UNIFESP), São Paulo, BrazilDepartment of Psychobiology, Universidade Federal de São Paulo (UNIFESP), São Paulo, BrazilFAPESP: 2010/07994-3FAPESP: 2015/03354-3CNPq/MS/SCTIE/DECIT: 26/2014CNPq/MS/SCTIE/DECIT: 466805/2014-4Web of Scienc

Effect of exposure prolonged the light and repetitive administration of melatonin in animal model of late dyskinesia

Doenca por vezes irreversivel, caracterizada por movimentos involuntarios (principalmente orofaciais) e supostamente consequente de uma supersensibilidade de dopaminoceptores pos-sinapticos estriatais, compensatoria ao bloqueio imposto pelos neuroiepticos, a discinesia tardia nao se desenvolve em todos os pacientes tratados com essas drogas - fato que sugere a participacao de fatores ainda desconhecidos no estabelecimento dessa sindrome. A busca e o estudo desses fatores poderiam, portanto, trazer novos subsidios ao entendimento de sua fisiopatologia (ainda controversa) bem como sugerir a possibilidade de tratamentos eficazes (inexistentes ate o momento). Entre os fatores capazes de modificar a plasticidade dopaminergica incluem-se o cicio clarolescuro e o hormonio meiatonina, inibido pela exposicao a luz. Em nosso estudo, procuramos verificar os efeitos da exposicao ininterrupta a luz ou da administracao prolongada de melatonina sobre dois modelos animais tradicionais de discinesia tardia: o registro da atividade geral (ATG) e da estereotipia (EST) induzida pela apomorfina em ratos privados da administracao prolongada de haloperidol, bem como sobre um novo modelo, recentemente proposto: o registro dos movimentos orofaciais (MOFS) induzidos pela administracao repetida de reserpina. Os tres modelos animais utilizados foram efetivos em evidenciar a supersensibilidade comportamental, uma vez que, em relacao aos respectivos controles, ratos privados de haloperidoi apresentaram aumentos significantes tanto na ATG como na EST induzida por apomorfina, enquanto que ratos tratados com reserpina exibiram uma maior intensidade de MOFS. Em relacao aos animais mantidos em um ciclo claro/escuro, a exposicao ininterrupta a luz aumentou significantemente a ATG e os MOFs tanto dos animais supersensiveis (tratados com haloperidol ou reserpina), como dos animais dos respectivos grupos controle (privados de veiculo). Por outro lado, o aumento proporcional da ATG e dos MOFs em relacao aos respectivos grupos controle, mantidos sob o mesmo ciclo, foi significantemente menor nos ratos expostos a um ciclo claro/claro. Dessa forma, a exposicao ininterrupta a luz aumentou a expressao da supersensibilidade comportamental mas diminuiu seu desenvolvimento. Por outro lado, os efeitos estimulantes motores da exposicao a luz nao foram observados para a EST induzida por apomorfina. Uma vez que este comportamento, ao contrario dos anteriores, nao depende da disponibilidade da...(au)BV UNIFESP: Teses e dissertaçõe

Role of striatal dopaminergic supersensitivity and oxidative stress in the development of orofacial dyskinesias: a comparative study between Wistar EPM-1 rats and spontaneously hypertensive rats(SHR)

Doenca por vezes irreversivel e consequente do tratamento prolongado com drogas neurolepticas classicas, a discinesia tardia caracteriza-se por apresentar, predominantemente, movimentos orofaciais discineticos. O principal fator de risco para o desenvolvimento dessa sindrome e o envelhecimento, que tambem promove o desenvolvimento de discinesia orofacial espontanea, fenomeno logicamente similar a discinesia tardia. A fisiopatologia da discinesia tardia ainda nao esta estabelecida, mas tanto a supersensibilidade dopaminergica nigroestriatal quanto o estresse oxidativo tem sido sugeridos como mecanismos responsaveis por seu desenvolvimento. Paralelamente, o estresse oxidativo e uma conhecida caracteristica do envelhecimento cerebral. Recentemente verificamos que a linhagem de animais espontaneamente hipertensos SHR (spontaneously hypertensive rats) nao desenvolve movimentos orofaciais induzidos por reserpina, um modelo animal de discinesia tardia. Esse achado parece revestir-se de especial importancia quando consideramos que apenas 20 por cento a 30 por cento dos individuos tratados com neurolepticos classicos desenvolvem discinesia tardia. Com efeito, ratos SHR e pacientes resistentes a discinesia tardia poderiam compartilhar caracteristicas neurofisiologicas que limitassem o desenvolvimento de discinesias orofaciais. Como primeiro objetivo desta tese, procuramos verificar se essa linhagem desenvolveria discinesia orofacial induzida tanto pelo envelhecimento quanto por um tratamentoBV UNIFESP: Teses e dissertaçõe

Cannabidiol, among other cannabinoid drugs, modulates prepulse inhibition of startle in the SHR animal model: implications for schizophrenia pharmacotherapy

Schizophrenia is a severe psychiatric disorder that involves positive, negative and cognitive symptoms. Prepulse inhibition of startle reflex (PPI) is a paradigm that assesses the sensorimotor gating functioning and is impaired in schizophrenia patients as well as in animal models of this disorder. Recent data point to the participation of the endocannabinoid system in the pathophysiology and pharmacotherapy of schizophrenia. Here, we focus on the effects of cannabinoid drugs on the PPI deficit of animal models of schizophrenia, with greater focus on the SHR (Spontaneously Hypertensive Rats) strain, and on the future prospects resulting from these findings

Sleep rebound attenuates context-dependent behavioural sensitization induced by amphetamine

We have recently demonstrated that paradoxical sleep deprivation (PSD) potentiates the induction of amphetamine (AMPH)-induced behavioural sensitization by increasing its conditioned component. in the present study, the effects of sleep rebound (induced by 24 h recovery period from PSD) were studied on AMPH-induced behavioural sensitization. Sleep rebound attenuated the acute locomotor-stimulating effect of AMPH. AMPH-induced behavioural sensitization was context-specific and was also attenuated by sleep rebound. These results strengthen the notion that sleep conditions can influence AMPH-incluced behavioural sensitization. (C) 2008 Elsevier Inc. All rights reserved.Universidade Federal de São Paulo, Dept Psychobiol, BR-04023062 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Pharmacol, BR-04023062 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Psychobiol, BR-04023062 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Pharmacol, BR-04023062 São Paulo, BrazilWeb of Scienc