RESUMO
BACKGROUND AND OBJECTIVE: Recent evidence suggests that the use of fluoxetine could reduce periodontal disease severity. However, the effect of fluoxetine on periodontal disease has not been tested in the context of conditioned fear stress (CFS). We hypothesized that inhibition of chronic stress by fluoxetine might decrease the levels of bone loss in periodontal disease. The aim of the present study was to analyze the effect of fluoxetine on bone loss in chronic periodontitis. MATERIAL AND METHODS: Fourteen Wistar rats were submitted to ligature-induced periodontal disease and divided into four groups (A-D). Groups A (n = 3) and B (n = 4) were not stressed, while Groups C (n = 3) and D (n = 4) were submitted to a CFS paradigm for 38 d. Daily fluoxetine (20 mg/kg) was administered to Groups B and D from day 20 to day 39, at which point the rats were submitted to an open field test and killed on day 40. Mandibles were removed for histological and immunohistochemical analyses. RESULTS: Stress was associated with a higher level of bone loss in Group C compared with Group A. Additionally, no differences in bone loss were observed among Groups A, B and D. CONCLUSION: We showed that stress is associated with the progression of bone loss in a CFS model in rats and that fluoxetine treatment reduces the bone loss.
Assuntos
Periodontite Crônica/prevenção & controle , Medo/psicologia , Fluoxetina/uso terapêutico , Inibidores Seletivos de Recaptação de Serotonina/uso terapêutico , Estresse Psicológico/psicologia , Perda do Osso Alveolar/patologia , Perda do Osso Alveolar/prevenção & controle , Perda do Osso Alveolar/psicologia , Animais , Ansiedade/psicologia , Periodontite Crônica/patologia , Periodontite Crônica/psicologia , Condicionamento Psicológico , Modelos Animais de Doenças , Progressão da Doença , Reação de Congelamento Cataléptica/fisiologia , Interleucina-1beta/análise , Interleucina-6/análise , Locomoção/efeitos dos fármacos , Masculino , Ratos , Ratos WistarRESUMO
BACKGROUND AND OBJECTIVE: Stress and anxiety have been associated with chronic periodontitis, but few studies examining the effects of psychotropic drugs on periodontal health have been performed. Therefore, we aimed to investigate the effects of diazepam on the progression of periodontitis in chronically stressed rats. MATERIAL AND METHODS: Fourteen Wistar rats were submitted to ligature-induced periodontal disease and were divided into four groups . Two groups were not stressed, whereas two groups were submitted to a conditioned fear stress paradigm for 38 d. Daily diazepam treatment (2 mg/kg, orally) was administered to one unstressed group and to one group submitted to a conditioned fear stress paradigm from day 2 to the day 39, at which point the rats were submitted to an open field test and were killed on day 40. Brains and mandibles were removed for histological and immunohistochemical analyses. RESULTS: Animals exposed to conditioned fear stress presented an increase in freezing behavior, a decrease in locomotor activity, enhanced alveolar bone loss and higher levels of hippocampal interleukin-1beta (IL-1ß) and interleukin-6 (IL-6), compared with the control group. Diazepam, at the dose used in the current study, had no effect on freezing behavior but reversed the decrease in locomotor activity provoked by stress. Additionally, the treatment reduced the levels of hippocampal IL-1ß and IL-6 and alveolar bone loss in Wistar rats. Neither conditioned fear stress nor diazepam treatment had an effect on periodontal IL-1ß or IL-6 levels in animals. CONCLUSION: Our results suggest that diazepam treatment reduces bone loss in rats submitted to conditioned fear stress. In addition, diazepam treatment led to decreased IL-1ß and IL-6 levels in the hippocampus.
Assuntos
Perda do Osso Alveolar/prevenção & controle , Ansiolíticos/uso terapêutico , Diazepam/uso terapêutico , Medo/fisiologia , Hipocampo/metabolismo , Interleucina-1beta/análise , Interleucina-6/análise , Perda do Osso Alveolar/metabolismo , Animais , Ansiolíticos/administração & dosagem , Condicionamento Operante , Diazepam/administração & dosagem , Progressão da Doença , Medo/psicologia , Reação de Congelamento Cataléptica/fisiologia , Hipocampo/patologia , Locomoção/fisiologia , Masculino , Ligamento Periodontal/metabolismo , Ligamento Periodontal/patologia , Periodontite/prevenção & controle , Periodontite/psicologia , Ratos , Ratos Wistar , Estresse Psicológico/metabolismo , Estresse Psicológico/psicologiaRESUMO
Nitric oxide synthase (NOS) accounts for most of the NADPH-diaphorase neuronal activity in the brain. NADPH-diaphorase-positive neurones have been localized at the dorso-lateral part of the periaqueductal grey (PAG), a region related to anxiety. Microinjections of the NOS inhibitors L-NAME (10-200 nmol 0.5 microliter-1) and L-NOARG (10-100 nmol) at this site induced anxiolytic-like effects in the elevated plus maze. These effects, however, occurred only at a limited range of doses and the dose-effect curve had a bell shape, higher doses of both compounds tending to be anxiogenic. The anxiolytic effect of L-NAME was antagonized by a previous microinjection of L-arginine (50 nmol 0.5 microliter-1). These results suggest that NO may play a role in PAG neurotransmission involved in anxiety.
Assuntos
Aminoácido Oxirredutases/antagonistas & inibidores , Ansiolíticos/farmacologia , Arginina/análogos & derivados , Óxido Nítrico/antagonistas & inibidores , Substância Cinzenta Periaquedutal , Animais , Arginina/administração & dosagem , Arginina/farmacologia , Comportamento Exploratório/efeitos dos fármacos , Histocitoquímica , Masculino , Microinjeções , NADPH Desidrogenase/metabolismo , NG-Nitroarginina Metil Éster , Neurônios/enzimologia , Óxido Nítrico Sintase , Nitroarginina , Substância Cinzenta Periaquedutal/citologia , Substância Cinzenta Periaquedutal/enzimologia , Ratos , Ratos WistarRESUMO
1. In order to assess the presence of anxiolytic properties in cannabidiol (CBD) derivatives HU-219, HU-252 and HU-261, these drugs were tested in rats submitted to the elevated plus-maze model of anxiety. 2. Additional groups received diazepam or CBD. HU-219 (0.03-1 mg/kg) and CBD (5 mg/kg) significantly increased the percentage of open arm entries without changing the total number of entries, an anxiolytic-like effect. 3. Both HU-252 and HU-261 increased the percentage of time spent in open arms and the total number of entries, but only at the dose of 1 mg/kg. 4. Diazepam (2.5 mg/kg) increased both the percentage of entries and time spent on open arms and the total number of entries. 5. The results confirm previous findings with CBD and indicate that its derivative HU-219 may possess a similar anxiolytic-like profile. 6. Results from HU-252 and HU-261 are less apparent and suggest that the compounds may increase general exploratory activity in a limited range of doses.
Assuntos
Ansiolíticos/farmacologia , Comportamento Animal/efeitos dos fármacos , Canabidiol/análogos & derivados , Animais , Canabidiol/farmacologia , Diazepam/farmacologia , Masculino , Ratos , Ratos WistarRESUMO
Studies with electrical brain stimulation suggest that the dorsal periaqueductal grey matter (DPAG) is related to anxiety and to the anti-aversive effects of benzodiazepines (BZD) compounds. However, direct stimulation of the brain may prevent conclusions about the role of specific regions in the control of normal behaviour. In the present study we employed the elevated plus-maze, an ethologically based model of anxiety, to investigate the role of BZD receptors located in the DPAG in anxiety and in the anxiolytic effect of systemically injected BZD. The results showed that midazolam (20-80 nmol), a BZD agonist, dose-dependently increased the percentage of entries and time spent in open arms when microinjected into the DPAG. The effect of midazolam (80 nmol) was antagonized by flumazenil (80 nmol), a BZD antagonist, microinjected into the DPAG 10 min before the agonist. FG 7142 (20-80 nmol), a BZD partial inverse agonist, decreased time spent in open arms at the dose of 40 nmol and the number of open arms entries at all doses when microinjected into the DPAG. The microinjection of flumazenil (80 nmol) into the DPAG failed to antagonize the anxiolytic effect of systemically injected diazepam (2.5 mg/kg). These results strengthen the idea of an involvement of BZD receptors located in the DPAG with anxiety. They also suggest that the DPAG is not the only structure responsible for the anxiolytic effects of systemically injected BZD.
Assuntos
2-Amino-5-fosfonovalerato/análogos & derivados , Ansiedade/fisiopatologia , Substância Cinzenta Periaquedutal/fisiopatologia , Receptores de GABA-A/efeitos dos fármacos , Aminoácidos/farmacologia , Animais , Anticonvulsivantes/farmacologia , Ansiedade/tratamento farmacológico , Ansiedade/psicologia , Depressores do Apetite/farmacologia , Carbolinas/farmacologia , Diazepam/farmacologia , Relação Dose-Resposta a Droga , Comportamento Exploratório/efeitos dos fármacos , Flumazenil/farmacologia , Masculino , Microinjeções , Midazolam/antagonistas & inibidores , Midazolam/farmacologia , Substância Cinzenta Periaquedutal/metabolismo , Ratos , Ratos WistarRESUMO
Plasmodium falciparum-infected erythrocytes (PfE) were collected from acutely infected children in The Gambia and Tanzania and cultured for more than 30 hr until the parasites were mature trophozoites. Sera collected from these countries, other African countries, Asia, and South America were used in the PfE microagglutination test to determine whether PfE from East and West Africa share surface antigens. From the patterns of agglutination reactivity, we identified extensive antigenic diversity in surface antigens, but obtained no evidence for greater differences between isolates from East or West Africa and those within one region. The majority of sera from immune adults from The Gambia, Tanzania, Sudan, Nigeria, or Ghana were pan-agglutinating, and agglutinated all PfE isolates from The Gambia and Tanzania. Some sera from immune adults of Irian Jaya also agglutinated each of the seven African isolates, while others agglutinated many but not all of the isolates, similar to sera from immune adults of Flores, Indonesia. In contrast, sera from nonimmune adults from Colombia agglutinated few of the African isolates. It was remarkable, however, that sera from nonimmune Colombians agglutinated any African isolates. Our results are consistent with the following conclusions: some PfE surface antigen(s) are very diverse; this diversity is a feature of the parasite worldwide; the repertoire of isolate-specific surface antigens, although large, includes antigens that are either identical or antigenically cross-reactive in geographically very distant parasite populations; and African adults have pan-agglutinating antibodies that may contribute to protective immunity. Such pan-agglutinating antibodies could reflect the accumulation of a large repertoire of isolate-specific antibodies. The contribution of antibody against any shared PfE surface antigen to the pan-agglutinating reactivities is unknown and awaits development of the appropriate reagents.
Assuntos
Antígenos de Protozoários/imunologia , Antígenos de Superfície/imunologia , Testes de Hemaglutinação , Malária Falciparum/imunologia , Plasmodium falciparum/imunologia , Adolescente , Adulto , África Oriental , África Ocidental , Animais , Sudeste Asiático , Criança , Colômbia , Eritrócitos/parasitologia , Humanos , Malária Falciparum/sangue , Pessoa de Meia-Idade , Plasmodium falciparum/classificaçãoRESUMO
In order to investigate the role of the dorsal periaqueductal grey (DPAG) area in the anxiolytic effect of benzodiazepines male Wistar rats (N = 10), weighing 200-250 g at the time of surgery, were microinjected into this structure with midazolam (80 nmol) and submitted to the elevated plus-maze, an ethologically based model of anxiety. Midazolam significantly increased the percentage of open arm entries from 32.4 +/- 4.6 (control) to 49.5 +/- 3.0 and of time spent in the open arms from 21.0 +/- 4.5 (control) to 35.6 +/- 4.8 without affecting the total number of entries into either open or enclosed arms. This effect typifies an anxiolytic effect in the test and was antagonized by the benzodiazepine receptor antagonist flumazenil (80 nmol) microinjected into the same site 10 min before the midazolam (80 nmol) microinjection. Microinjection of flumazenil alone had no effect. These results provide additional evidence for the participation of the DPAG in the physiopathology of anxiety and suggest that it may be a site for the anxiolytic effect of systemically injected benzodiazepines.
Assuntos
Ansiedade/induzido quimicamente , Comportamento Animal/efeitos dos fármacos , Midazolam/farmacologia , Substância Cinzenta Periaquedutal/efeitos dos fármacos , Análise de Variância , Animais , Sinergismo Farmacológico , Estimulação Elétrica , Flumazenil/administração & dosagem , Flumazenil/farmacologia , Masculino , Microinjeções , Midazolam/administração & dosagem , Midazolam/antagonistas & inibidores , Substância Cinzenta Periaquedutal/fisiologia , Ratos , Ratos EndogâmicosRESUMO
In order to localise the often reported anxiolytic action of N-methyl-D-aspartate (NMDA) receptor antagonists, 2-amino-7-phosphonoheptanoic acid (AP7) was injected into the dorsal periaqueductal grey (DPAG) of rats exposed to the elevated plus-maze model of anxiety. Doses of 0.2, 2 and 20 nmol AP7 caused a dose-dependent increase in the percentage of open arm entries, the effect of the last two doses being significantly different from control. A non-significant tendency to increase the percentage of time spent on the open arms of the maze was also noticed. In contrast, the total number of entries into either the open or enclosed arms was not affected. Injections of AP7 localized outside the DPAG were ineffective. Therefore, microinjection of AP7 into the DPAG caused a selective anxiolytic effect in the elevated plus-maze. It may be suggested that the DPAG is a site of the anxiolytic action of NMDA antagonists reported following systemic administration.
Assuntos
2-Amino-5-fosfonovalerato/análogos & derivados , Aminoácidos/farmacologia , Ansiolíticos , Receptores de N-Metil-D-Aspartato/antagonistas & inibidores , Animais , Comportamento Animal/efeitos dos fármacos , Encéfalo/anatomia & histologia , Relação Dose-Resposta a Droga , Comportamento Exploratório/efeitos dos fármacos , Masculino , Mesencéfalo , Microinjeções , Substância Cinzenta Periaquedutal , Ratos , Ratos EndogâmicosRESUMO
In order to investigate the role of the dorsal periaqueductal grey (DPAG) area in the anxiolytic effect of benzodiazepines male Wistar rats (N=10), weighing 200-250 g at the time of surgery, were microinjected into this structure with midazolam (80 nmol) and submitted to the elevated plus-maze, an ethologically based model of anxiety. Midazolam significantly increased the percentage of open arm entries from 32.4 ñ 4.6 (control) to 49.5 ñ 3.0 and of time spent in the open arms from 21.0 ñ 4.5 (control) to 35.6 ñ4.8 without affecting the total number of entries into either open or enclosed arms. This effect typifies an anxiolytic effect in the test and was antagonized by the benzodiazepine receptor antagonist flumazenil (80 nmol) microinjection. Microinjection of flumazenil alone had no effect. These results provide additional evidence for the participation of the DPAG in the physiopathology of anxiety and suggest that it that it may be a site for the anxiolytic effect of systemically injected benzodiazepines
Assuntos
Animais , Ratos , Masculino , Ansiedade/induzido quimicamente , Comportamento Animal/efeitos dos fármacos , Midazolam/farmacologia , Substância Cinzenta Periaquedutal/efeitos dos fármacos , Análise de Variância , Sinergismo Farmacológico , Estimulação Elétrica , Flumazenil/administração & dosagem , Flumazenil/farmacologia , Microinjeções , Midazolam/administração & dosagem , Midazolam/antagonistas & inibidores , Substância Cinzenta Periaquedutal/fisiologia , Ratos WistarRESUMO
Previously reported results indicate that serotonin (5-HT) inhibits the neural sub strate of aversion in the dorsal midbrain central grey (DCG) of the rat. In addition, the present results show that microinjection of the 5-HT uptake inhibitor zimelidine (100 nmol) into the DCG of rats with chronically implanted chemitrodes raised the threshold of aversive electrical stimulation. This antiaversive effect of zimelidine was antagonized by pretreatment with the 5-HT(2) receptor blocker ritanserin (10 nmol), also microinjected into the DCG. In contrast, the antiaversive effect of the benzodiazepine agonist midazolam (40 nmol) was unaffected by ritanserin. Propranolol (2.2, 4.4 and 8.8 nmol) raised the aversive threshold in a dose-depen dent way following its injection into the DCG. The antiaversive effect of 4.4 nmol of propranolol was antagonized by previous administration of ritanserin (10 nmol). Moreover, combined administration of zimelidine (100 nmol) followed by propranolol (4.4 nmol) caused an anti aversive effect which was equivalent to the sum of the effect of each drug alone. These results indicate that the antiaversive effect of intracerebrally injected zimelidine and propranolol is mediated by endogenous 5-HT, through activation of 5-HT(2) receptors.
Assuntos
Lactente , Pré-Escolar , Criança , Adolescente , Humanos , Masculino , Feminino , Enteropatias Parasitárias , Nematoides , Brasil , Infecções por NematoidesRESUMO
1. Electrical stimulation of the dorsal periaqueductal gray matter (DPAG), an aversive area of the rat brain, increased the mean blood pressure of awake rats as well as of animals anesthetized with urethane. 2. In the anesthetized rats, increases in heart rate and in breath rate were also induced by DPAG stimulation. 3. Chlordiazepoxide, a benzodiazepine, decreased the blood pressure rise caused by aversive stimulation of the brain in the awake rat. 4. Chlordiazepoxide elicited the same effect in urethane-anesthetized rats. In addition, the hyperpnea induced by electrical stimulation of the dorsal periaqueductal gray matter was also decreased by the drug. 5. The pressor response to intravenous noradrenaline was not affected by chlordiazepoxide. 6. These results suggest that benzodiazepines attenuate the neurovegetative changes accompanying emotion by depressing brain systems that integrate emotional behavior.