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Contradictory findings suggest that the behavioral and abuse-related effects of ethanol are mediated by its action at α1 subunit-containing GABAA (α1GABAA) receptors. In the present study, we investigated the effects of a sub-chronic post-ethanol administration treatment with zolpidem, an α1-preferring positive allosteric modulator at GABAA receptors, on the subsequent expression of ethanol-induced behavioral sensitization in mice. Animals received ethanol (1.8 g/kg, ip) or saline treatments every other day for 15 days (8 treatment sessions) and were subsequently treated with zolpidem (0.5 mg/kg, ip) or vehicle 4 times on alternate days. At the end of the treatment phase, animals were challenged with saline or ethanol on separate days for the evaluation of the expression of conditioned locomotion and behavioral sensitization. Eight-day treatment with ethanol did not lead to the development of ethanol-induced behavioral sensitization. Animals treated with ethanol and subsequently administered vehicle showed similar locomotion frequencies during the last ethanol challenge compared to the control group receiving ethanol for the first time. Animals treated with ethanol and subsequently administered zolpidem expressed behavioral sensitization to ethanol during the ethanol challenge. The present study adds to the literature by providing further evidence of a role of α1GABAA receptors on the behavioral effects of ethanol. Because of the current highly prevalent co-abuse of ethanol and benzodiazepine drugs in humans, the use of zolpidem and other α1GABAA receptor ligands during ethanol withdrawal should be monitored carefully.

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Contradictory findings suggest that the behavioral and abuse-related effects of ethanol are mediated by its action at α1 subunit-containing GABAA (α1GABAA) receptors. In the present study, we investigated the effects of a sub-chronic post-ethanol administration treatment with zolpidem, an α1-preferring positive allosteric modulator at GABAA receptors, on the subsequent expression of ethanol-induced behavioral sensitization in mice. Animals received ethanol (1.8 g/kg, ip) or saline treatments every other day for 15 days (8 treatment sessions) and were subsequently treated with zolpidem (0.5 mg/kg, ip) or vehicle 4 times on alternate days. At the end of the treatment phase, animals were challenged with saline or ethanol on separate days for the evaluation of the expression of conditioned locomotion and behavioral sensitization. Eight-day treatment with ethanol did not lead to the development of ethanol-induced behavioral sensitization. Animals treated with ethanol and subsequently administered vehicle showed similar locomotion frequencies during the last ethanol challenge compared to the control group receiving ethanol for the first time. Animals treated with ethanol and subsequently administered zolpidem expressed behavioral sensitization to ethanol during the ethanol challenge. The present study adds to the literature by providing further evidence of a role of α1GABAA receptors on the behavioral effects of ethanol. Because of the current highly prevalent co-abuse of ethanol and benzodiazepine drugs in humans, the use of zolpidem and other α1GABAA receptor ligands during ethanol withdrawal should be monitored carefully.

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RATIONALE: We have previously demonstrated that treatment with ziprasidone and aripiprazole selectively inhibit the development of behavioral sensitization to cocaine in mice. We now investigate their effects on a counter-conditioning strategy in mice and the importance of the treatment environment for this phenomenon. OBJECTIVE: Evaluate the context-specificity of ziprasidone and aripiprazole on conditioned locomotion to cocaine and cocaine-induced hyperlocomotion and behavioral sensitization in a counter-conditioning strategy in mice. METHODS: Animals were sensitized with saline or cocaine injections in the open-field apparatus in a 15-day intermittent treatment and subsequently treated with vehicle, 5mg/kg ziprasidone or 0.1mg/kg aripiprazole paired to the open-field or the home-cage for 4 alternate days. Mice were then challenged with saline and cocaine in the open-field apparatus on subsequent days. RESULTS: While treatment with ziprasidone decreased spontaneous locomotion and conditioned locomotion alike, treatment with aripiprazole specifically attenuated the expression of conditioned hyperlocomotion to cocaine. Ziprasidone and aripiprazole had no effects on cocaine-induced conditioned hyperlocomotion observed during saline challenge after drug withdrawal. Treatment with either ziprasidone or aripiprazole when previously given in the cocaine-paired environment attenuated the subsequent expression of behavioral sensitization to cocaine. Animals treated with aripiprazole in the open-field, but not in the home-cage, showed a blunted response to cocaine when receiving a cocaine challenge for the first time. CONCLUSIONS: Both neuroleptic drugs showed a context-dependent effectiveness in attenuating long-term expression of cocaine-induced behavioral sensitization when administered in the cocaine-associated environment, with aripiprazole also showing effectiveness in blocking the expression of acute cocaine effects.

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BACKGROUND: Hallucinogenic drugs were used to treat alcoholic patients in the past, and recent developments in the study of hallucinogens led to a renewal of interest regarding the application of these drugs in the treatment of addiction. In this scenario, accumulating evidence suggests that the hallucinogenic brew ayahuasca (Aya) may have therapeutic effects on substance abuse problems. METHODS: We investigated the effects of Aya on spontaneous locomotor activity and ethanol(Eth)-induced hyperlocomotion and subsequent locomotor sensitization by a two-injection protocol. Additionally, we tested the effect of Aya on an 8-day counter-sensitization protocol to modify sensitized responses induced by a repeated treatment with Eth (1.8g/kg) for 8 alternate days. RESULTS: Aya showed high sensitivity in preventing the development of Eth-induced behavioral sensitization, attenuating it at all doses (30, 100, 200, 300 or 500 mg/kg) without modifying spontaneous locomotor activity. At the highest doses (300 and 500 mg/kg), Aya also showed selectivity to both acute and sensitized Eth responses. Finally, a counter-sensitization strategy with 100 or 300 mg/kg of Aya for 8 consecutive days after the establishment of Eth-induced behavioral sensitization was effective in blocking its subsequent expression on an Eth challenge. CONCLUSIONS: We demonstrated that Aya not only inhibits early behaviors associated with the initiation and development of Eth addiction, but also showed effectiveness in reversing long-term drug effects expression, inhibiting the reinstatement of Eth-induced behavioral sensitization when administered in the Eth-associated environment.

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Viable metacyclic forms of T. cruzi, Y strain, treated with an adequate dose of actinomycin D (50 micrograms Act-D/ml/10(7) parasites/ml for 72 h at 28 degrees C) showed the following properties: 1) they lost their ability to replicate in culture medium, in blood and in tissues of normal mice and were no longer able to incorporate tritiated thymidine; 2) they could not penetrate into Vero cells and could not replicate inside normal macrophages; 3) they retained their immunogenicity and the ability to protect mice against a virulent infection; 4) they did not induce histological lesions as described in chronic experimental Chagas' disease.

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The subcutaneous (s.c.) vaccination of DBA/2 mice with 4 weekly doses of 3 x 10(7) living metacyclic forms of T. cruzi, Y strain, obtained from culture in axenic medium and treated for 24 h with actinomycin-D (50 micrograms/10(7) parasites), a drug that promotes an irreversible blockade of the parasite replication, do not induce any detectable degree of humoral and cellular immunosuppression as assessed by a) the production of anti-SRBC antibodies, b) the permanence of delayed cutaneous reaction to T. cruzi antigen, to PPD and DNCB and c) the degree of blastogenic transformation of spleen lymphocytes in the presence of the specific antigen.

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The main steps of a sensitive and quantitative technique for the simultaneous determination, in the same microplate, of antigen, antibody and specific immune complexes has been described. The assay involved principles of the double sandwich technique used in the "Enzyme-Linked Immunosorbent Assay" (ELISA). The technique proved to be useful for the estimation of antigen, antibody and specific immune complexes in sera of patients with human chronic hepato-intestinal schistosomiasis.

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Viable BCG bacilli, in a lipid emulsion, inoculated intravenously, were capable of reverting the profound humoral immunosuppression induced in adult DBA/2 mice by the mastocytoma P-815. BCG increased not only the number of hemolytic plaque forming cells, but also the serum titers of hemagglutinating IgM antibodies. However, no blocking effect was detected on normal tumor progression.

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The pattern of surface density and distribution of Langerhans Cells (LC) in the Swiss Webster (SW) albino mouse is reported. LC were demonstrated using ATP-Pb and their densities evaluated in the skin of anterior and posterior foot-pads, tail, abdomen, back and ear. Cells were counted using a light microscope with a drawing tube by projecting 0.01 mm2 areas at 150X magnification. The distribution and density of LC were quite different in the various regions of SW mouse skin.

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A vaccine prepared from killed and sonicated promastigotes of five Brazilian strains of Leishmania was used during an epidemic of American dermal leishmaniasis that occurred in Viana county, State of Espírito Santo, Brazil. Initially, all of the participants in the vaccination programme had negative reactions to Montenegro antigen. Forty days after the last dose of vaccine had been given, 87.6% of the 216 vaccinated individuals had become Montenegro-positive whereas the 266 unvaccinated persons remained Montenegro-negative. The study area had an unstable population and details are given about the human population changes that occurred during the two-year study period. Taking into account population movements, 1.5% of those vaccinated and 6.4% of the unvaccinated group developed dermal leishmanial lesions by the end of the first year. At the end of the second year, 1.7% of those vaccinated and 8.9% of the unvaccinated group had become infected. The difference in infection rates of the two groups is statistically significant at both the end of the first and second years of observation. Diagnosis of the disease(s) was based on the clinical appearance of lesions combined with parasitological and/or immunological evidence and subsequent responses to treatment. The experience gained in Viana also provided information about the storage and administration of the experimental vaccine which have been used in mounting a randomized clinical trial.

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Twenty children, with the diagnosis of cerebral palsy (CP) and under classical, physiotherapeutical and pedagogical, treatment, received piracetam (pyrrolidine acetamide) as an auxiliary drug. The goal was to better spasticity, learning and nervous instability problems aiming at better results of over-all treatment of CP. The group that received the drug has been compared to a control group of 20 children treated by the customary treatment only. The comparison showed favourable results for the medicated group. The drug was administered in the dose of 80 mg/kg/day during 10 weeks. The criteria for evaluation have been psychological, clinical, physiotherapeutical and pedagogical. The drug has been given in a new form of presentation: 6% solution for oral use.

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