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1.
Mol Psychiatry ; 21(8): 1137-44, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-26728562

RESUMO

Social cognition enables individuals to understand others' intentions. Social memory is a necessary component of this process, for without it, subsequent encounters are devoid of any historical information. The CA2 area of the hippocampus, particularly the vasopressin 1b receptor (Avpr1b) expressed there, is necessary for memory formation. We used optogenetics to excite vasopressin terminals, originating from the hypothalamic paraventricular nucleus, in the CA2 of mice. This markedly enhanced their social memory if the stimulation occurred during memory acquisition, but not retrieval. This effect was blocked by an Avpr1b antagonist. Finally, this enhanced memory is resistant to the social distraction of an introduced second mouse, important for socially navigating populations of individuals. Our results indicate the CA2 can increase the salience of social signals. Targeted pharmacotherapy with Avpr1b agonists or deep brain stimulation of the CA2 are potential avenues of treatment for those with declining social memory as in various dementias.


Assuntos
Região CA2 Hipocampal/metabolismo , Receptores de Vasopressinas/metabolismo , Agressão/fisiologia , Animais , Arginina Vasopressina , Hipocampo/metabolismo , Masculino , Memória/fisiologia , Camundongos , Optogenética/métodos , Receptores de Vasopressinas/genética , Comportamento Social
3.
Transl Psychiatry ; 4: e447, 2014 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-25247592

RESUMO

Antidepressant medication constitutes the first line pharmacological treatment for posttraumatic stress disorder (PTSD), however, because many patients display no beneficial drug effects it has been suggested that combinations of antidepressants with additional drugs may be necessary. The defining symptoms of PTSD include re-experiencing, avoidance and hyperarousal. In addition, PTSD patients were shown to become easily distracted and often suffer from poor concentration together with indications of comorbidity with attention-deficit hyperactivity disorder (ADHD). Methylphenidate (MPH) is the most common and effective drug treatment for ADHD, thus we aimed to investigate the effects of MPH treatment, by itself or in combination with the antidepressants fluoxetine (FLU) or desipramine (DES). We modified an animal model of PTSD by exposing rats to chronic stress and evaluating the subsequent development of behavioral PTSD-like symptoms, as well as the effects on proinflammatory cytokines, which were implicated in PTSD. We report that while FLU or DES had a beneficial effect on avoidance and hyperarousal symptoms, MPH improved all three symptoms. Moreover, the combination of MPH with DES produced the most dramatic beneficial effects. Serum levels of interleukin-1ß (IL-1ß) and IL-6 were elevated in the PTSD-like group compared with the control group, and were decreased by MPH, FLU, DES or the combination drug treatments, with the combination of DES+MPH producing the most complete rescue of the inflammatory response. Considering the versatile symptoms of PTSD, our results suggest a new combined treatment for PTSD comprising the antidepressant DES and the psychostimulant MPH.


Assuntos
Antidepressivos Tricíclicos/farmacologia , Estimulantes do Sistema Nervoso Central/farmacologia , Desipramina/farmacologia , Metilfenidato/farmacologia , Transtornos de Estresse Pós-Traumáticos/tratamento farmacológico , Animais , Modelos Animais de Doenças , Quimioterapia Combinada , Masculino , Ratos , Ratos Wistar , Resultado do Tratamento
4.
Neuroscience ; 253: 1-8, 2013 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-23973403

RESUMO

Sleep is an essential physiological process that underlies crucial cognitive functions as well as emotional reactivity. Thus, sleep deprivation (SD) may exert various deleterious effects. In this study, we aimed to examine the adverse behavioral and hormonal effects of SD and a potential treatment with Plant-derived nanoparticle treatment - cocc 30c. The study was a 4-arm trial with randomization and double-blinding of verum and placebo treatments. SD was induced by using the Multiple Platform Method for 48 h. The effects of SD were evaluated behaviorally (pre-pulse inhibition (PPI), startle response and rotor-rod) at baseline as well as at 6, 12, 24h, and 14 days post deprivation. cocc 30c treatment was administrated Per Os every three hours starting immediately after baseline tests and for a period of 24h. On day 14, blood samples were taken and serum levels of corticosterone, testosterone, serotonin and leptin were tested. We found that cocc 30c improved PPI 12 and 24h post deprivation, likewise, cocc 30c improved motor learning. On day 14 SD led to increased startle response that was ameliorated by cocc 30c. Likewise, SD led to increased levels of corticosterone and serotonin while decreasing testosterone and leptin. Interestingly, cocc 30c treatment has moderated these hormonal alterations. We conclude that the treatment with cocc 30c recovers both short-term behavioral and the long-term hormonal modulations following SD.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Transtornos dos Movimentos/tratamento farmacológico , Nanopartículas/uso terapêutico , Fitoterapia/métodos , Privação do Sono/complicações , Estimulação Acústica , Animais , Transtorno do Deficit de Atenção com Hiperatividade/etiologia , Cocculus/química , Modelos Animais de Doenças , Método Duplo-Cego , Masculino , Transtornos dos Movimentos/etiologia , Extratos Vegetais/uso terapêutico , Ratos , Ratos Wistar , Tempo de Reação/efeitos dos fármacos , Reflexo de Sobressalto/efeitos dos fármacos , Privação do Sono/sangue , Sono REM/efeitos dos fármacos , Fatores de Tempo
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