Is the antidepressant effect of ketamine separate from its psychotomimetic effect? A review of rodent models.

Ketamine is an NMDA (N-methyl-d-aspartate) glutamate receptor antagonist, which has a myriad of dose-dependent pharmacological and behavioral effects, including anesthetic, sedative, amnestic, analgesic, and anti-inflammatory properties. Intriguingly, ketamine at subanesthetic doses displays a relevant profile both in mimicking symptoms of schizophrenia and also as the first fast-acting treatment for depression. Here, we present an overview of the state-of-the-art knowledge about ketamine as an antidepressant as well as a pharmacological model of schizophrenia in animal models and human participants. Ketamine's dual effect appears to arise from its mechanism of action involving NMDA receptors, with both immediate and downstream consequences being triggered as a result. Finally, we discuss the feasibility of a unified approach linking the glutamatergic hypothesis of schizophrenia to the promising preclinical and clinical success of ketamine in the treatment of refractory depression.

Beneficial effects of exercise training (treadmill) on insulin resistance and nonalcoholic fatty liver disease in high-fat fed C57BL/6 mice.

C57BL/6 mice develop signs and symptoms comparable, in part, to the human metabolic syndrome. The objective of the present study was to evaluate the effects of exercise training on carbohydrate metabolism, lipid profile, visceral adiposity, pancreatic islet alterations, and nonalcoholic fatty liver disease in C57BL/6 mice. Animals were fed one of two diets during an 8-week period: standard (SC, N = 12) or very high-fat (HF, N = 24) chow. An exercise training protocol (treadmill) was then established and mice were divided into SC and HF sedentary (SC-Sed, HF-Sed), exercised groups (SC-Ex, HF-Ex), or switched from HF to SC (HF/SC-Sed and HF/SC-Ex). HF/HF-Sed mice had the greatest body mass (65% more than SC/SC-Sed; P < 0.0001), and exercise reduced it by 23% (P < 0.0001). Hepatic enzymes ALP (+80%), ALT (+100%) and AST (+70%) were higher in HF/HF mice than in matched SC/SC. Plasma insulin was higher in both the HF/HF-Sed and HF/SC-Sed groups than in the matched exercised groups (+85%; P < 0.001). Pancreatic islets, adipocytes and liver structure were greatly affected by HF, ultimately resulting in islet beta-cell hypertrophy and severe liver steatosis. The HF group had larger islets than the SC/SC group (+220%; P < 0.0001), and exercise significantly reduced liver steatosis and islet size in HF. Exercise attenuated all the changes due to HF, and the effects were more pronounced in exercised mice switched from an HF to an SC diet. Exercise improved the lipid profile by reducing body weight gain, visceral adiposity, insulin resistance, islet alterations, and fatty liver, contributing to obesity and steatohepatitis control.

Beneficial effects of exercise training (treadmill) on insulin resistance and nonalcoholic fatty liver disease in high-fat fed C57BL/6 mice

C57BL/6 mice develop signs and symptoms comparable, in part, to the human metabolic syndrome. The objective of the present study was to evaluate the effects of exercise training on carbohydrate metabolism, lipid profile, visceral adiposity, pancreatic islet alterations, and nonalcoholic fatty liver disease in C57BL/6 mice. Animals were fed one of two diets during an 8-week period: standard (SC, N = 12) or very high-fat (HF, N = 24) chow. An exercise training protocol (treadmill) was then established and mice were divided into SC and HF sedentary (SC-Sed, HF-Sed), exercised groups (SC-Ex, HF-Ex), or switched from HF to SC (HF/SC-Sed and HF/SC-Ex). HF/HF-Sed mice had the greatest body mass (65 percent more than SC/SC-Sed; P < 0.0001), and exercise reduced it by 23 percent (P < 0.0001). Hepatic enzymes ALP (+80 percent), ALT (+100 percent) and AST (+70 percent) were higher in HF/HF mice than in matched SC/SC. Plasma insulin was higher in both the HF/HF-Sed and HF/SC-Sed groups than in the matched exercised groups (+85 percent; P < 0.001). Pancreatic islets, adipocytes and liver structure were greatly affected by HF, ultimately resulting in islet â-cell hypertrophy and severe liver steatosis. The HF group had larger islets than the SC/SC group (+220 percent; P < 0.0001), and exercise significantly reduced liver steatosis and islet size in HF. Exercise attenuated all the changes due to HF, and the effects were more pronounced in exercised mice switched from an HF to an SC diet. Exercise improved the lipid profile by reducing body weight gain, visceral adiposity, insulin resistance, islet alterations, and fatty liver, contributing to obesity and steatohepatitis control.

Impairment of cytomegalovirus-specific cellular immune response as a risk factor for cytomegalovirus disease in transplant recipients: [review]

Human cytomegalovirus (CMV) infection is common in most people but nearly asymptomatic in immunocompetent individuals. After primary infection the virus persists throughout life in a latent form in a variety of tissues, particularly in precursor cells of the monocytic lineage. CMV reinfection and occurrence of disease are associated with immunosuppressive conditions. Solid organ and bone marrow transplant patients are at high risk for CMV disease as they undergo immunosuppression. Antiviral treatment is effective in controlling viremia, but 10-15 percent of infected patients can experience CMV disease by the time the drug is withdrawn. In addition, long-term antiviral treatment leads to bone marrow ablation and renal toxicity. Furthermore, control of chronic CMV infection in transplant recipients appears to be dependent on the proper recovery of cellular immunity. Recent advances in the characterization of T-cell functions and identification of distinct functional signatures of T-cell viral responses have opened new perspectives for monitoring transplant individuals at risk of developing CMV disease.

Impairment of cytomegalovirus-specific cellular immune response as a risk factor for cytomegalovirus disease in transplant recipients.

Human cytomegalovirus (CMV) infection is common in most people but nearly asymptomatic in immunocompetent individuals. After primary infection the virus persists throughout life in a latent form in a variety of tissues, particularly in precursor cells of the monocytic lineage. CMV reinfection and occurrence of disease are associated with immunosuppressive conditions. Solid organ and bone marrow transplant patients are at high risk for CMV disease as they undergo immunosuppression. Antiviral treatment is effective in controlling viremia, but 10-15% of infected patients can experience CMV disease by the time the drug is withdrawn. In addition, long-term antiviral treatment leads to bone marrow ablation and renal toxicity. Furthermore, control of chronic CMV infection in transplant recipients appears to be dependent on the proper recovery of cellular immunity. Recent advances in the characterization of T-cell functions and identification of distinct functional signatures of T-cell viral responses have opened new perspectives for monitoring transplant individuals at risk of developing CMV disease.

Effects of ayahuasca on psychometric measures of anxiety, panic-like and hopelessness in Santo Daime members.

The use of the hallucinogenic brew ayahuasca, obtained from infusing the shredded stalk of the malpighiaceous plant Banisteriopsis caapi with the leaves of other plants such as Psychotria viridis, is growing in urban centers of Europe, South and North America in the last several decades. Despite this diffusion, little is known about its effects on emotional states. The present study investigated the effects of ayahuasca on psychometric measures of anxiety, panic-like and hopelessness in members of the Santo Daime, an ayahuasca-using religion. Standard questionnaires were used to evaluate state-anxiety (STAI-state), trait-anxiety (STAI-trait), panic-like (ASI-R) and hopelessness (BHS) in participants that ingested ayahuasca for at least 10 consecutive years. The study was done in the Santo Daime church, where the questionnaires were administered 1h after the ingestion of the brew, in a double-blind, placebo-controlled procedure. While under the acute effects of ayahuasca, participants scored lower on the scales for panic and hopelessness related states. Ayahuasca ingestion did not modify state- or trait-anxiety. The results are discussed in terms of the possible use of ayahuasca in alleviating signs of hopelessness and panic-like related symptoms.

Anxiogenic effects in the rat elevated plus-maze of 5-HT(2C) agonists into ventral but not dorsal hippocampus.

The effect of the non-selective 5-HT2C receptor agonist trifluoromethyl-phenylpiperazine (TFMPP, 0.75, 1.5 and 3.0 microg) and the preferential 5-HT2C agonist 6-chloro-2(1-piperazinyl)pyrazine (MK-212, 0.1, 0.3 and 1.0 microg) microinjected into the ventral or dorsal hippocampus was investigated in anxiety measures of rats exposed to the elevated plus-maze test. Ventral hippocampal (VH) microinjections of the 0.75 or 1.5 microg doses of TFMPP reduced open-arm exploration without affecting the number of closed-arm entries, indicating a selective anxiogenic profile. The highest dose (3.0 microg) reduced open- and closed-arm entries, suggesting interference in locomotor activity. The 0.1 microg dose of MK-212 also caused a selective anxiogenic effect when microinjected into the ventral hippocampus, without disturbing locomotor activity. Microinjections of the two higher doses of MK-212 (0.3 or 1.0 microg) into the ventral hippocampus led to a decrease of exploration in both arms of the maze. In contrast to the anxiogenic effect observed in the VH, neither TFMPP nor MK-212 significantly changed anxiety measures when microinjected into the dorsal hippocampus. These results suggest that activation of 5-HT2C postsynaptic receptors located in the ventral, but not in the dorsal, hippocampus play an important role in anxiety triggered by the elevated plus-maze test.

Neuroanatomical and neuropharmacological study of opioid pathways in the mesencephalic tectum: effect of mu(1)- and kappa-opioid receptor blockade on escape behavior induced by electrical stimulation of the inferior colliculus.

Deep layers of the superior colliculus (DLSC), the dorsal and ventral periaqueductal gray matter (PAG), and inferior colliculus (IC) are midbrain structures involved in the generation of defensive behavior. beta-Endorphin and Leu-enkephalin are some neurotransmitters that may modulate such behavior in mammals. Light microscopy immunocytochemistry with streptavidin method was used for the localization of the putative cells of defensive behavior with antibodies for endogenous opioids in rat brainstem. Midbrain structures showed positive neurons to beta-endorphin and Leu-enkephalin in similar distributions in the experimental animals, but we also noted the presence of varicose fibers positive to endogenous opioids in the PAG. Neuroanatomical techniques showed varicose fibers from the central nucleus of the inferior colliculus to ventral aspects of the PAG, at more caudal levels. Naloxonazine and nor-binaltorphimine, competitive antagonists that block mu(1)- and kappa-opioid receptors, were then used in the present work to investigate the involvement of opioid peptide neural system in the control of the fear-induced reactions evoked by electrical stimulation of the neural substrates of the inferior colliculus. The fear-like responses were measured by electrical stimulation of the central nucleus of the inferior colliculus, eliciting the escape behavior, which is characterized by vigorous running and jumping. Central administration of opioid antagonists (2.5 microg/0.2 microl and 5.0 microg/0.2 microl) was performed in non-anesthetized animals (Rattus norvegicus), and the behavioral manifestations of fear were registered after 10 min, 2 h, and 24 h of the pretreatment. Naloxonazine caused an increase of the defensive threshold, as compared to control, suggesting an antiaversive effect of the antagonism on mu(1)-opioid receptor. This finding was corroborated with central administration of nor-binaltorphimine, which also induced a decrease of the fear-like responses evoked by electrical stimulation of the inferior colliculus, since the threshold of the escape behavior was increased 2 and 24 h after the blockade of kappa-opioid receptor. These results indicate that endogenous opioids may be involved in the modulation of fear in the central nucleus of the inferior colliculus. Although the acute treatment (after 10 min) of both naloxonazine and nor-binaltorphimine causes nonspecific effect on opioid receptors, we must consider the involvement of mu(1)- and kappa-opioid receptors in the antiaversive influence of the opioidergic interneurons in the dorsal mesencephalon, at caudal level, after chronic (2-24 h) treatment of these opioid antagonists. The neuroanatomical study of the connections between the central nucleus of the inferior colliculus and the periaqueductal gray matter showed neuronal fibers with varicosities and with terminal bottons, both in the pericentral nucleus of the inferior colliculus and in ventral and dorsal parts of caudal aspects of the periaqueductal gray matter.

Ethopharmacological analysis of 5-HT ligands on the rat elevated plus-maze.

The present study investigated the behavioral effects of five 5-HT agonists and antagonists in the rat elevated-plus-maze using conventional and ethologically derived measures. An anxiolytic effect of the 5-HT1A agonist ipsapirone (0.25, 0.75, and 2.25 mg/kg) was detected by risk-assessment and scanning but not by percentage of open-arm entries and time spent on open arms. Anxiogenic effects of the 5-HT2C agonist TFMPP (0.1, 0.2, and 0.4 mg/kg) and 5-HT2A antagonist SR 46349B (1, 3, and 10 mg/kg) were detected by percentage of open-arm entries, time spent on open arms, scanning, end exploring, but not by risk assessment. Finally, the effects of the 5-HT3 antagonist BRL 46470 A (0.001, 0.01, and 0.1 mg/kg) and 5-HT(2A/C) antagonist RP 62203 (0.25, 1, and 4 mg/kg) were scarce in both conventional and ethologically derived measures. These results are indicative that ethological measures may sometimes be more sensitive than the standard ones, and should be used together with them when assessing serotonergic or any other novel drugs in the elevated plus-maze.

Intraaortic balloon pump support during coronary angioplasty. Initial experience.

OBJECTIVE: To evaluate the use of the intraaortic balloon (IAoB) in association with coronary angioplasty in high-risk patients. METHODS: Fourteen high-risk patients unresponsive to clinical therapy and with formal contraindication to surgical revascularization were treated by coronary angioplasty, most of which was followed by stenting. All procedures were performed with circulatory support with the IAoB. This study reports the early results and the late findings after 12 months of follow-up. Six patients had multivessel coronary disease; of these, four had left main equivalent lesions and two had unprotected left main coronary artery disease, one of whom had severe "end-vessel" stenosis and the other was a patient with Chagas' disease with single-vessel lesion. Eleven patients had a left ventricular ejection fraction < 30%. RESULTS: In 100% of the patients, the procedures were initially successful. Two patients had severe bleeding during the withdrawal of the left femoral sheath. At the end of twelve months, 4 patients were asymptomatic and the others were clinically controlled. There were two late deaths in the 7th and 11th months. CONCLUSION: The combined use of the intraaortic balloon pump and percutaneous coronary angioplasty in high-risk patients with acute ischemic syndromes provides the necessary hemodynamic stability to successfully perform the procedures.

Efeito da palpaçäo retal e da freqüência de inseminaçöes na fertilidade de éguas inseminadas com sêmen fresco diluído / Effect of rectal palpation and frequency of inseminations on fertility of inseminated mares with fresh diluted semen

Estudaram-se os efeitos da palpaçäo retal e da freqüência de inseminaçöes sobre a fertilidade de 42 éguas inseminadas, ou em dias alternados, com sêmen de apenas um garanhäo, diluído no diluidor de mínima contaminaçäo. Utilizou-se um delineamento inteiramente casualizado com número igual de repetiçöes, em um esquema fatorial 3 x 2, com três freqüências de palpaçäo retal (6/6 h, 12/12 e uma vez ao dia). E duas de inseminaçäo (diárias ou em dias alternados). Sistema de palpaçäo retal näo afetou as taxas de concepçäo ao primeiro ciclo, concepçäo/cio e concepçäo total, nem a eficiência de prenhez obtida, independentemente de freqüência de inseminaçäo utilizada. Näo se observou influência da freqüência de palpaçäo sobre as seguintes características: ciclos/égua, ciclos/éguas gestante, ciclos/prenhez, prenhez/ciclo, número de IA/égua, número de IA/égua gestante e número de IA/égua vazia. A freqüência de inseminaçöes näo afetou as taxas de concepçäo ao primeiro ciclo, concepçäo/ciclo, concepçäo total, nem a eficiência de prenhez. O número de IA/égua, número de IA/égua gestante e número de IA/égua vazia diferiram em relaçäo à freqüência de inseminaçöes, com os maiores valores observados no grupo de éguas inseminadas diariamente. Recomenda-se a utilizaçäo de inseminaçöes em dias alternados. Palpaçöes retais a cada 6 horas podem ser realizadas sem deprimir a fertilidade

Effects of microinjections of mu and kappa receptor agonists into the dorsal periaqueductal gray of rats submitted to the plus maze test.

Several lines of evidence have shown that aversive states are under the influence of opioid mechanisms in the dorsal periaqueductal gray (DPAG). In order to characterize the type of opioid receptors involved in these effects in this work we injected DAMGO and U50,488H, mu and kappa selective agonists, respectively, directly in this structure. Rats implanted with chemitrode in the DPAG were submitted to the elevated plus maze test for 5 min. The effects of DAMGO (0.1-1 nmol/0.2 microliter) and U50,488H (1-10 nmol/0.2 microliter) following administration into DPAG were studied. Low doses of DAMGO (0.1 and 0.3 nmol) caused dose-dependent increases in the number of entries and time spent in the open arms while an overall deficit in the exploratory activity was produced by the higher dose used (1.0 nmol). Clear aversive effects were observed following the administration of U50,488H in the DPAG. The antiaversive effects of 0.3 nmol DAMGO were inhibited by the intraperitoneal administration of the mu receptor antagonist naltrexone (2.0 mg/kg, IP) whereas the aversive effects of 5.0 nmol U50,488H were antagonized by the selective kappa receptor antagonist nor-binaltorphimine (1.0 mg/kg, IP). It is suggested that activation of mu receptors inhibit and kappa receptors enhance the neural substrate of aversion in the DPAG.

Behavioral and pharmacological validation of the elevated plus maze constructed with transparent walls.

In this study we compared the performance of male Wistar rats, weighing 250-300 g, submitted to the standard plus maze (vertical surfaces of the closed arms with opaque walls) to their performance in a modified maze with raised Plexiglas edges in the closed arms (transparent walls). The animals (N = 12 for each group) continued to show a clear preference for the closed arms with transparent walls of the modified elevated plus maze. In addition, exploratory activity was higher in the open arms of the modified plus maze (4.25 +/- 0.42 entries and 53.50 +/- 5.10 s) as compared to that of the standard plus maze (2.10 +/- 0.25 entries and 24.00 +/- 4.91 s). Intraperitoneal injection of midazolam produced an increase in the number of entries (6.40 +/- 1.21 and 8.50 +/- 1.15 for 1.0 and 2.0 mg/kg, respectively) and in the time spend in the open arms (85.32 +/- 14.56 and 125.50 +/- 22.16 s for 1.0 and 2.0 mg/kg, respectively) while pentylenetetrazole caused a decrease in the number of entries (3.68 +/- 0.54 and 2.33 +/- 0.62 for 5.0 and 10 mg/kg, respectively) and in the time spent in the open arms of the modified maze (39.60 +/- 6.67 and 23.60 +/- 6.40 s for 5.0 and 10 mg/kg, respectively). The anxiolytic effect of midazolam and the anxiogenic effect of pentylenetetrazole were similar to those usually reported in the literature by authors using the standard test. These results behaviorally and pharmacologically validate the elevated plus maze with transparent walls and suggest that this test could be a useful tool for the study of anxiolytic drugs and the neurobiology of anxiety.

Behavioral and pharmacological validation of the elevated plus maze contructed with transparent walls

In this study we compared the performance of male Wistar rats, weighing 250-300g, submitted to the standard plus maze (vertical surfaces of the closed arms with opaque walls) to their performance in a modified maze with raised Plexiglas edges in the closed arms (transparent walls). The animals (N = 12 for each group) continued to show a clear preference for the closed arms with transparent walls of the modified elevated plus maze. In addition, exploratory activity was higher in the open arms of the modified plus maze (4.25 ñ 0.42 entries and 53.50 ñ 5.10s) as compared to that of the standard plus maze (2.10 ñ 0.25 entries and 24.00 ñ 4.91 s). Intraperitoneal injection of midazolam produced an increase in the number of entries (6.40 ñ 1.21 and 8.50 ñ 1.15 for 1.0 and 2.0 mg/Kg, rspectively) and in the time spent in the open arms (85.32 ñ 14.56 and 125.50 ñ 22.16 s for 1.0 and 2.0 mg/Kg, respectively) while pentylenetetrazole caused a decrease in the number of entries (3.68 ñ 0.54 and 2.33 ñ 0.62 for 5.0 and 10 mg/Kg, respectively) and in the time spent in the open arms of the modified maze (39.60 ñ 6.67 and 23.60 ñ 6.40 s for 5.0 and 10 mg/Kg, respectively). The anxiolytic effect of midazolam and the anxiogenic effect of pentylenetetrazole were similar to those usually reported in the literature by authors using the standard test. The4se results behaviorally and pharmacologically validate the elevated plus maze with transparebnt walls and suggest that this test could be a useful tool for the study of anxiolytic drugs and the neurobiology of anxiety

Neural substrate of defensive behavior in the midbrain tectum.

It has been shown that the gradual increase in the intensity of electrical stimulation of the dorsal periaqueductal gray (DPAG), deep layers of the superior colliculus (DLSC) and inferior colliculus of rats induces, in a progressive manner, characteristic aversive responses such as arousal, freezing, and escape behavior. The DPAG-DLSC together with the periventricular gray substance of the diencephalon, amygdala and the inferior colliculus, constitute the neural substrate of aversion in the brain. In general, the behavioral responses induced by midbrain tectum stimulation are accompanied by increases in the mean arterial blood pressure, heart rate, and respiration. Both the behavioral and autonomic consequences of electrical stimulation of the mesencephalic tectum have been shown to be attenuated by minor tranquilizers, probably through enhancement of GABAergic neurotransmission. Besides GABAergic mechanisms several lines of evidence have clearly implicated opioid, serotonergic, and excitatory amino acids-mediated mechanisms in the control of the neural substrates commanding defensive behavior in the brain aversive system.

Mutagenic activity detected by the Ames test in river water under the influence of petrochemical industries.

The present study was carried out on the waters of the Caí River (Rio Grande do Sul, Brazil) in an area under the influence of a petrochemical industrial complex, as the continuation of a study in which the mutagenic activity of water samples was evaluated in the internal area of this complex. In the previous study, the release of inducing substances was detected, revealing the need for a full analysis of the real ecological impact of the industrial complex on the river. Water samples from different sites along the Caí River were subjected to the Ames test during a study of 20 months duration for the detection of possible mutagens. Strains TA100 and TA98 were used for initial sample screening in the presence and absence of the S9 mix at a standard dose of 2000 microliters/plate. When positive activity (values equal to twice the spontaneous mutation rate) and/or cytotoxic activity (cell survival below 60%) was detected, the dose-response relationship was studied. Thirty-four percent of the samples tested were mutagenic, with different values according to collection site. Of the total number of positive responses, 6% were obtained for samples collected at the blank site upstream from the area studied, 82% at sites closest to the industrial complex, and 12% in downstream areas. Strain TA98 was the most sensitive in assays with no metabolic activation. A low frequency of induction (2%) was observed for strain TA102. Application of the Ames test permitted the delimitation of three areas of influence of the petrochemical industrial complex, and the test proved to be adequate for the detection of contaminants from the petrochemical industry.

Aversive and antiaversive effects of morphine in the dorsal periaqueductal gray of rats submitted to the elevated plus-maze test.

The dorsal periaqueductal gray (DPAG) is a well-known region for processing defensive behavior in the brainstem. Rats implanted with cannulae in the DPAG were submitted to the elevated plus-maze test for 5 min. The effects of morphine following systemic (0.1-1.0 mg/kg) or DPAG administration (5-30 nmol) were compared with the benzodiazepine compound midazolam injected similarly (1-10 mg/kg, IP, and 10-80 nM, DPAG). Morphine and midazolam caused dose-dependent increases in the number of entries and time spent in the open arms. A systemic injection of naloxone in doses that block mu-opioid receptors reversed the effects of centrally administered morphine. Higher doses of morphine (70 nmol) induced a non-naloxone-reversible "fearful" hyperreactivity. It is suggested that low doses of morphine inhibit the neural substrate of aversion in the DPAG, probably through activation of mu-receptors, and that microinjections of higher doses of morphine cause proaversive actions not mediated by these opioid receptors.

Effects of blockade of 5-HT2 receptors and activation of 5-HT1A receptors on the exploratory activity of rats in the elevated plus-maze.

Acute administration of gepirone, a 5-HT1A agonist, caused a dose dependent (1-10 mg/kg, IP) reduction in the locomotor activity (open and closed arms) of rats tested in the elevated plus-maze. However, rats housed in individual cages and submitted to chronic treatment with gepirone (10 mg/kg PO) showed a marked increase in the percentages of number and time spent in the open arms as compared to controls. These results are compatible with the idea that the antiaversive effect due to long-term treatment with 5-HT1A agonists is the result of a progressive desensitization of the somatodendritic 5-HT autoreceptor with the consequent recovery of firing rate of 5-HT neurons along with an activation of normosensitive postsynaptic 5-HT neurons. Ketanserin caused a biphasic effects on the exploratory behavior of rats in the plus-maze. The lower dose (0.5 mg/kg) decreased the aversion to the open arms and the higher dose (1.0 mg/kg) caused an unspecific decrease in the overall activity of the animals. Ketanserin is supposed to have antagonistic action on 5-HT2 and on alpha-adrenergic receptors. As prazosin (0.5-1.0 mg/kg), an alpha-adrenergic receptor blocker, did not present any significant effect in the present work it is suggested that the effects of the lower dose of ketanserin was due to its high antagonistic action on 5-HT2 receptors.

Mutagenic and genotoxic effects of aqueous extracts of Achyrocline satureoides in prokaryotic organisms.

Aqueous extracts of Achyrocline satureoides (Marcela and/or Macela) were tested for the presence of genotoxic activity in microorganisms. This species belongs to the family Compositae and is used on a large scale by the population of South Brazil. The extracts showed genotoxic activity in the presence of S9 mix in the Ames test TA100, TA98 and TA102 strains, 'SOS' spot chromotest and Microscreen phage-induction assay. The positive results were related to the presence of quercetin and caffeic acid in the aqueous extracts.

Analysis of mutagenicity of waters under the influence of Petrochemical Industrial Complexes by the Ames test (Salmonella microsome)

Water samples within the area of the II Petrochemical Industrial Complex (pluvial draining accumulation, safety basins and industrial effluent) and at different points along the Caí river were tested for the presence of mutagens and/or carcinogens using the Ames test. Positive results were obtained for the TA 100 an TA 98 strains with or without microsomal activation in samples within the area of the Petrochemical Industrial Complex and at the Caí river sampling sites closest to the industrial complex. These results suggest the presence of mutagens causing frameshift and base-pair substitution mutations, indicating the need for continuous monitoring of the area of influence of the III Petrochemical Industrial Complexo to evaluate the full environmental impact of this industrial complex