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Background: Studies have shown that acute ethanol exposure inhibits ionotropic glutamate receptor function and that long-term ethanol exposure results in maladaptive increases in the expression of some of these receptors in neurons. It has been postulated that these changes, when unopposed by ethanol, contribute, in part, to the hyperexcitability associated with ethanol withdrawal. In this study, we compared the effect of long-term ethanol exposure on the hippocampal expression levels of subunits belonging to the three families of ionotropic glutamate receptors., Methods: Adult male Sprague-Dawley rats were fed an ethanol-containing diet for 16 days. This diet contained 0% ethanol on days 1 and 2, 3% on days 3 and 4, 5% on days 5 to 7, and 6.7% on days 8 to 16. Control rats received an equivalent amount of an isocaloric diet without ethanol. Rats were killed on day 16 at the peak of ethanol consumption. Hippocampal homogenates were prepared by sonication and analyzed by Western immunoblotting techniques. On a separate group of rats, we measured withdrawal scores and audiogenic seizures on day 17., Results: Ethanol-exposed rats had significantly higher withdrawal scores, and a significantly higher percentage of them developed audiogenic seizures; this indicates that the 16-day ethanol diet induces ethanol dependence. Unexpectedly, we found that expression of NR1 (including the expression of NR1 subunits containing the N1, C1, and C2 inserts), NR2A, NR2B, NR2C, GluR1, GluR2/3, GluR5, GluR6/7, and KA2 subunits was not altered in hippocampal homogenates from ethanol-exposed rats., Conclusions: These results indicate that maladaptive changes in the hippocampal expression levels of ionotropic glutamate receptor subunits do not always occur in ethanol-dependent rats. Consequently, other mechanisms must mediate the hyperexcitability state associated with ethanol withdrawal in these animals.

The influence of peripheral benzodiazepine receptor ligands Ro5-4864 (0.05 or 1.0 mg/kg, i.p.) or PK11195 (0.05 or 1.0 mg/kg, i.p.) on the anxiolytic effect of ethanol (1.2 g/kg; 14% p/v; i.p.) was investigated in rats tested on the elevated plus-maze. Other animals were injected through intrahippocampal administrations of the ligands (0.5 or 1.0 nmol/0.5 &mgr;l) before ethanol (1.2g/kg; 14% p/v; i.p.) and submitted to the elevated plus-maze test. The results showed that the systemic administration of either ligands 24 hours before the ethanol treatment resulted in a reduced anxiolytic effect of this drug. Only PK11195 reversed the effect of ethanol after intrahippocampal injection. These data suggest that peripheral benzodiazepine receptors play a role in ethanol anxiolysis.

The actions of ethanol on brain ligand-gated ion channels have important roles in the pathophysiology of alcohol-related neurodevelopmental disorders and fetal alcohol syndrome. Studies have shown that N-methyl-d-aspartate (NMDA) receptors are among the ligand-gated ion channels affected by prenatal ethanol exposure. We exposed pregnant dams to an ethanol-containing liquid diet that results in blood ethanol levels near the legal intoxication limit in most states (0.08%). Primary cultures of hippocampal neurons were prepared from the neonatal offspring of these dams, and NMDA receptor function was assessed by patch clamp electrophysiological techniques after 6-7 days in culture in ethanol-free media. Unexpectedly, we did not detect any changes in hippocampal NMDA receptor function at either the whole-cell or single-channel levels. However, we determined that fetal alcohol exposure alters the actions of the neurosteroids pregnenolone sulfate and pregnenolone hemisuccinate, which potentiate NMDA receptor function. Western immunoblot analyses demonstrated that this alteration is not due to a change in the expression levels of NMDA receptor subunits. Importantly, in utero ethanol exposure did not affect the actions of neurosteroids that inhibit NMDA receptor function. Moreover, the actions of pregnenolone sulfate on type A gamma-aminobutyric acid and non-NMDA receptor function were unaltered by ethanol exposure in utero, which suggests that the alteration is specific to NMDA receptors. These findings are significant because they provide, at least in part, a plausible mechanistic explanation for the alterations in the behavioral responses to neurosteroids found in neonatal rats prenatally exposed to ethanol and to other forms of maternal stress (Zimmerberg, B., and McDonald, B. C. (1996) Pharmacol. Biochem. Behav. 55, 541-547).

The effects of intraperitoneal and intrahippocampal administration of the glucocorticoid dexamethasone were assessed regarding ethanol-induced anxiolysis in the elevated plus-maze in rats. Animals pretreated with systemic injections of dexamethasone (0.5, 1. 0, or 2.0 mg/kg, IP) 15 min before ethanol (1.2 g/kg, 14% w/v, IP) administration showed a significant dose-dependent attenuation of the increased percentage of frequency and time spent on open arms of the maze. However, IP dexamethasone treatment 4 h before the test had no effect. Unilateral intrahippocampal injection of dexamethasone (2 and 20 nmol in 0.5 microl) also significantly attenuated the increased exploration of the open arms induced by ethanol. The results are interpreted in terms of the modulation of the anxiolytic effects of ethanol by glucocorticoids and the possible involvement of hippocampus in this response. The rapid blockade of ethanol induced anxiolysis by dexamethasone strengthens the suggestion that a nongenomic mechanism may underlie this response.

Objective: The underreporting of AIDS cases in the municipality of Rio de Janeiro, Brazil, is significant. The study intends to analyze the factors associated to this event., Methods: Using data provided by the Hospital Information System for the year of 1996, in Rio de Janeiro city, and by the National Surveillance System, patients were randomly selected and their medical records reviewed to verify an AIDS diagnosis. A multinomial model was used to perform an analysis of the variations on the chances of underreporting of AIDS cases versus reporting and on the chances of underreporting without evidences to fulfill the case definition of AIDS versus reporting., Results: No significant associations were found between the variables such as "age", "marital status", "level of education", "occupation", and "severity of illness" and the underreporting of AIDS cases. The variable "female gender" showed a strong association with hospitalization without evidence of an AIDS diagnosis. A strong association was found between two or more admissions in an inpatient unit care and reporting. The existence of a epidemiological surveillance department in the hospital is inversely associated with the underreporting of AIDS cases., Conclusion: The significant association between organizational variables and underreporting of AIDS cases found in the study point out to the need of standardization of the surveillance procedures, the especial need for the creation and maintenance of surveillance departments in hospitals to improve the quality of the health information system and, therefore, AIDS prevention and care.

Background: Nitric oxide (NO) is a neuromodulator and an intercellular and retrograde messenger that mediates several functions in the central nervous system. The effects of ethanol (EtOH) on neuronal NO-dependent pathways have been the focus of recent research. Most studies have concentrated on the actions of chronic EtOH exposure. In this study, we examined the role of NO-dependent pathways in the acute actions of EtOH., Methods: We used the elevated plus-maze test to study the role of NO-dependent pathways in the behavior of rats treated with acute EtOH. We tested the effects of 7-nitroindazole, a reversible competitive inhibitor of nitric oxide synthase. We also studied the effects of the cyclic guanylate monophosphate (cGMP) analog, 8-Bromoguanosine cyclic 3',5'-monophosphate sodium salt, and the NO donors S-nitroso-N-acetylpenicillamine or sodium nitroprusside., Results: When injected by either intraperitoneal (6 mg/kg) or intrahippocampal (20 nmol) routes, 7-nitroindazole increased the percentage of open arm entries and time spent in open arms for rats injected with EtOH (1.0 g/kg, ip). This dose of EtOH did not produce an anxiolytic effect when administered alone. Additional experiments were performed with a dose of 1.2 g/kg of EtOH (ip), which produced an anxiolytic effect. Intrahippocampal administration of the cGMP analog, 8-Bromoguanosine cyclic 3',5'-monophosphate sodium salt (40 nmol), or the NO donors S-nitroso-N-acetylpenicillamine (20 or 40 nmol) or sodium nitroprusside (20 or 40 nmol) blocked the anxiolytic effect of this dose of EtOH., Conclusions: These results indicate that inhibition of NO-dependent pathways enhances, whereas stimulation of these pathways decreases, the efficacy of EtOH to produce anxiolytic effects in rats. We postulate that NO-dependent increases in guanylate cyclase activity and cGMP levels oppose the anxiolytic effects produced by acute EtOH administration.

Data from the Hospital Information System (SIH-SUS) were linked to data from the AIDS Case Reporting System (Sinan) to assess the level of under-reporting of AIDS cases in the city of Rio de Janeiro. A high level of unreported cases(42.7%) was observed for patients treated in hospitals under Brazil's Unified Health System in the city of Rio. Bivariate analysis showed an association between reporting to the Sinan and age, principal diagnosis, and type of hospital.

Previous studies from our laboratory have shown gender-related behavior in rats tested in the elevated plus-maze under the influence of ethanol and other drugs. The present study investigated the effects of pretreatment with the NMDA-receptor partial agonist at the glycine site D-cycloserine (DCS; doses 3 to 9 mg/kg for females; 3 to 12 mg/kg for males, intraperitoneally) on the effects of ethanol (1.2 g/kg, i.p.; 14% w/v) and (+/-)-3-amino-1-hydroxy-2-pyrrolidone (HA-966; 2 or 4 mg/kg, i.p.), an antagonist at the glycine site of the NMDA receptor complex in rats submitted to the elevated plus-maze test. The results showed that DCS, at doses that did not affect the behavior of control animals, significantly (p < 0.05) prevented the increase in the percentage of open-arm entries and the time spent in the open arms of elevated plus-maze test induced by ethanol, exhibiting a U-shaped dose-response curve. Similarly, DCS blocked the anxiolytic effects of HA-966 in animals of both gender. Data confirm our previous results, suggesting that the NMDA-receptor system contributes significantly to the anxiolytic effect of ethanol. Furthermore, the similarity between the blockade by DCS of anxiolysis induced either by ethanol or by HA-966 strengthens the suggestion that ethanol acts on the glycine site of the NMDA receptor complex.

The effect of dexamethasone on ethanol-induced hypothermia was investigated in 3.5-month old male Wistar rats (N = 10 animals per group). The animals were pretreated with dexamethasone (2.0 mg/kg, i.p.; volume of injection = 1 ml/kg) 15 min before ethanol administration (2.0, 3.0 and 4.0 g/kg, i.p.; 20% w/v) and the colon temperature was monitored with a digital thermometer 30, 60 and 90 min after ethanol administration. Ethanol treatment produced dose-dependent hypothermia throughout the experiment (-1.84 +/- 0.10, -2.79 +/- 0.09 and -3.79 +/- 0.15 degrees C for 2.0, 3.0 and 4.0 g/kg ethanol, respectively, 30 min after ethanol) but only the effects of 2.0 and 3.0 g/kg ethanol were significantly antagonized (-0.57 +/- 0.09 and -1.25 +/- 0.10, respectively, 30 min after ethanol) by pretreatment with dexamethasone (ANOVA, P < 0.05). These results are in agreement with data from the literature on the rapid antagonism by glucocorticoids of other effects of ethanol. The antagonism was obtained after a short period of time, suggesting that the effect of dexamethasone is different from the classical actions of corticosteroids.

Previous studies from our laboratory have demonstrated that male and female rats exhibit a differential pattern of behavior in the elevated plus-maze as a function of age. In the present study, the influence of individual housing conditions on young animals treated with one of two classical anxioselective drugs, diazepam or pentylenetetrazole, was investigated in the elevated plus-maze. In Experiment I, males and females were housed for 30 days after weaning either individually or in groups, and tested in the elevated plus-maze at 60 days of age. In Experiment 2, the effects of diazepam (0.75 or 1.0 mg/kg) or of pentylenetetrazole (20 or 30 mg/kg) on the behavior of isolated or grouped rats were studied at 60 days of age in the elevated plus-maze. The results show that isolated housed animals tested with diazepam at 60 days of age exhibited increased frequency and time spent on the open arms of the apparatus compared to control rats. The effect of diazepam was not observed in grouped animals tested at 60 days of age. Pentylenetetrazole produced a decrease in the frequency and time spent on the open arms. This effect was more prominent in grouped animals. The results suggest that 60-day-old rats deprived of playfighting experience present high basal anxiety levels and also that rearing conditions (isolated or grouped) are able to interact with both anxiolytic and anxiogenic effects of experimental drugs.

There is evidence that ethanol is able to influence central functions through the antagonism of the NMDA-receptor system. It has been shown that this system is also involved in the modulation of anxiety-related behavior in rats. Recently, we observed gender- and age-related behavioral influences in rats tested on the elevated plus-maze apparatus The present study was undertaken in order to investigate: (1) the effects of ethanol (0.8, 1.0 or 1.2 g/kg, i.p.) on the behavior of male and female rats tested on the elevated plus-maze at 2, 3, 4 or 5 months of age; (2) the effect of the pre-treatment with D-cycloserine (3.0 or 6.0 mg/kg), an agonist of the glutamate NMDA-receptor system, 30 min before the ethanol (1.2 g/kg) injections, in rats tested in the elevated plus-maze at 2 months or 4 months of age. The results demonstrated that ethanol did not affect the time spent and the frequency of entries on the open arms of the elevated plus-maze in rats tested at 2 months of age, but increased these parameters in older animals. Moreover, the results showed that D-cycloserine, at doses that did not affect the behavior of control animals, antagonized the increased frequency of entries and time spent on open arms produced by ethanol in rats tested at 4 months of age. Our results suggest an age-related influence on the anxiolytic action of ethanol in rats tested in the elevated plus-maze. Moreover, the results suggest that the NMDA-receptor system can be involved in this effect, and strengthens the evidence for the participation of the NMDA-receptor system in anxiety-related behavior.