Contamination of equipment and surfaces in the operating room anesthesia workspace: a cross-sectional study.

BACKGROUND: Contamination of the breathing circuit and medication preparation surface of an anesthesia machine can increase the risk of cross-infection. OBJECTIVE: To evaluate the contamination of the anesthetic medication preparation surface, respiratory circuits, and devices used in general anesthesia with assisted mechanical ventilation. DESIGN AND SETTING: Cross-sectional, quantitative study conducted at the surgical center of a philanthropic hospital, of medium complexity located in the municipality of Três Lagoas, in the eastern region of the State of Mato Grosso do Sul. METHODS: Eighty-two microbiological samples were collected from the breathing circuits. After repeating the samples in different culture media, 328 analyses were performed. RESULTS: A higher occurrence of E. coli, Enterobacter spp., Pseudomonas spp., Staphylococcus aureus, and Streptococcus pneumoniae (P < 0.001) were observed. Variations were observed depending on the culture medium and sample collection site. CONCLUSION: The study findings underscore the inadequate disinfection of the inspiratory and expiratory branches, highlighting the importance of stringent cleaning and disinfection of high-touch surfaces.

Contamination of equipment and surfaces in the operating room anesthesia workspace: a cross-sectional study

ABSTRACT BACKGROUND: Contamination of the breathing circuit and medication preparation surface of an anesthesia machine can increase the risk of cross-infection. OBJECTIVE: To evaluate the contamination of the anesthetic medication preparation surface, respiratory circuits, and devices used in general anesthesia with assisted mechanical ventilation. DESIGN AND SETTING: Cross-sectional, quantitative study conducted at the surgical center of a philanthropic hospital, of medium complexity located in the municipality of Três Lagoas, in the eastern region of the State of Mato Grosso do Sul. METHODS: Eighty-two microbiological samples were collected from the breathing circuits. After repeating the samples in different culture media, 328 analyses were performed. RESULTS: A higher occurrence of E. coli, Enterobacter spp., Pseudomonas spp., Staphylococcus aureus, and Streptococcus pneumoniae (P < 0.001) were observed. Variations were observed depending on the culture medium and sample collection site. CONCLUSION: The study findings underscore the inadequate disinfection of the inspiratory and expiratory branches, highlighting the importance of stringent cleaning and disinfection of high-touch surfaces.

Gastrointestinal stromal tumor of the excluded stomach after Roux-en-Y gastric bypass: A case report and literature review.

BACKGROUND: Gastric cancer is an extremely rare condition to occur after bariatric surgery, and most of the reported cases are adenocarcinomas. Regarding gastrointestinal stromal tumors (GISTs), there are only two reported cases occurring after bariatric surgery (one after gastric banding and the other following Roux-en-Y gastric bypass (RYGB)). CASE PRESENTATION: A 48-year-old woman with previous history of obesity and type 2 diabetes, treated with a Roux-en-Y gastric bypass 2 years earlier, was referred to our center due to complains of diffuse abdominal pain and distension associated with asthenia. Magnetic resonance imaging showed a cystic-solid mass located in the right hypochondrium, measuring 19.5 × 13.5 × 16 cm, suggesting the diagnosis of a retroperitoneal tumor. Based on these findings, a laparotomy, evidencing that the larger cystic-solid tumor was originating from the excluded stomach post-RYGB. The gastrectomy of the excluded stomach was performed aside with a conventional cholecystectomy. Histopathology and immunohistochemistry confirmed to be a gastric GIST with epithelioid cells. Currently, 12 months after surgery, the patient presents no signs of recurrence. CONCLUSION: This is the second case of gastric GIST occurring after RYGB to be reported in the literature.

Broad Diversity of Fungi in Hospital Water.

INTRODUCTION: Some studies have reported the occurrence of microorganisms isolated from water. Considering these microorganisms, fungi are known to occur ubiquitously in the environment, including water, and some are pathogenic and may cause health problems, especially in immunocompromised individuals. The aim of this study was to identify fungi in hospital water samples and to correlate their presence with the concentration of free residual chlorine. METHODS: Water samples (100 mL) were collected from taps (n = 74) and water purifiers (n = 14) in different locations in a university hospital. Samples were filtered through a nitrocellulose membrane and placed on Sabouraud dextrose agar and incubated for 24 hours at 30°C. Fungi were identified according to established methods based on macroscopic and microscopic characteristics (filamentous) and physiological tests (yeasts). Free chlorine residual content was measured at the time of sample collection. RESULTS: Seventy species of fungi were identified in the water samples and about 56% of the water samples contained culturable fungi. Cladosporium oxysporum, Penicillium spinulosum, and Aspergillus fumigatus were the most common filamentous fungi. Aureobasidium pullulans and Candida parapsilosis were the most common yeasts. Chemical analyses revealed that free residual chlorine was present in 81.8% of the samples within recommended concentrations. Among samples from water purifiers, 92.9% showed low levels of free residual chlorine (<0.2 mg/L). There was no significant association between chlorine concentrations (either within or outside the recommended range) and the presence of filamentous fungi and yeasts. CONCLUSIONS: This study showed that hospital water can be a reservoir for fungi, some of which are potentially harmful to immunocompromised patients. Free residual chlorine was ineffective in some samples.

Assessment of TCF7L2 expression after bariatric surgery.

OBJECTIVE: To assess the influence of bariatric surgery on transcription factor 7-like 2 (TCF7L2) expression and its association with body mass index (BMI) and Type 2 diabetes mellitus (T2DM). METHODS: Prospective study performed between 2016 and 2018, where 26 obese patients undergoing bariatric surgery were divided into two subgroups: diabetics and non-diabetics. The RNAs were extracted from peripheral blood samples that were obtained from each patient in two different moments: before surgery and after 12 months of follow-up. The relative expression of TCF7L2 was determined according to the delta-Ct method. RESULTS: The linear regression model of BMI x delta-Ct showed a positive correlation (p = 0.037). In the subgroups, an inversely proportional relationship was found between delta-Ct and BMI in the diabetic group and a directly proportional relationship in the non-diabetic group (p>0.05 in both). In the postoperative period, the regression model was similar to the preoperative, except when analyzing the subgroups, where diabetic patients showed a directly proportional relationship (p>0.05). The relative expression of TCF7L2 showed an average of 1.16 ± 0.91, CI-95% 0.79-1.53. There was an increase in relative expression of 48% in the non-diabetic group (p = 0.021), and a decrease of 27% in the T2DM group (p>0.05) in the postoperative. There was a positive correlation between a greater decrease in BMI and increased relative expression (p = 0.027). CONCLUSION: Our results showed that generally, the TCF7L2 expression increase with a decrease in BMI, however, for patients with T2DM, it exhibits an inverse pattern, which is normalized one year after bariatric surgery.

Analysis of the lipid profile of patients submitted to sleeve gastrectomy and Roux-en-Y gastric bypass. / Análise do perfil lipídico de pacientes submetidos à gastrectomia vertical e à derivação gástrica em Y de Roux.

OBJECTIVE: to compare the improvements in lipid profile in patients undergoing sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB). METHODS: in a mixed cohort study, we evaluated 334 patients undergoing SG and 178 patients undergoing RYGB at the University Hospital of the Federal University of Pernambuco and at the Real Hospital Português de Beneficência, Recife, PE, Brazil. We measured serum levels of total cholesterol, LDL, HDL and triglycerides preoperatively and at three, six, 12 and 24 months follow-up. RESULTS: the SG group consisted of 58 men and 276 women. In the group submitted to RYGB, there were 64 men and 114 women. The mean age was 37.2±20.5 years in the SG group and 41.9±11.1 years in the RYGB group. The preoperative mean BMI was 39.4±2.6kg/m2 and 42.7±5.8kg/m2 for the SG and RYGB groups, respectively. In the preoperative period, 80% of the patients had at least one abnormality in the lipid profile. Two years after surgery, there was improvement in total cholesterol, LDL, HDL and triglycerides in the group submitted to RYGB. In the group submitted to SG, after two years there was improvement in total cholesterol, HDL and triglyceride levels. CONCLUSION: both techniques resulted in improvements in the lipid profile, but the RYGB was more effective.

OBJETIVO: comparar as melhorias no perfil lipídico de pacientes submetidos à gastrectomia vertical (GV) e à derivação gástrica em Y de Roux (DGYR). METÓDOS: estudo de coorte misto, em que foram avaliados 334 pacientes submetidos à GV e 178 pacientes submetidos à DGYR no Hospital das Clínicas da Universidade Federal de Pernambuco e no Real Hospital Português de Beneficência, Recife, PE, Brasil. Foram realizadas dosagens séricas de colesterol total, LDL, HDL e triglicerídeos no pré-operatório e com três, seis, 12 e 24 meses de seguimento. RESULTADOS: o grupo submetido à GV foi composto por 58 homens e 276 mulheres. No grupo submetido à DGYR, foram analisados 64 homens e 114 mulheres. A média de idade foi de 37,2±20,5 anos no grupo da GV e de 41,9±11,1 anos no grupo da DGYR. O IMC médio pré-operatório foi de 39,4±2,6kg/m2 e 42,7±5,8kg/m2, para o grupo da GV e da DGYR, respectivamente. No pré-operatório, 80% dos pacientes tinha, no mínimo, uma anormalidade no perfil lipídico. Dois anos após a cirurgia houve melhora do colesterol total, LDL, HDL e triglicerídeos no grupo submetido à DGYR. No grupo submetido à GV, após dois anos houve melhora dos níveis de colesterol total, HDL e triglicerídeos, apenas. CONCLUSÃO: ambas as técnicas resultaram em melhorias no perfil lipídico, porém a DGYR foi mais efetiva.

Análise do perfil lipídico de pacientes submetidos à gastrectomia vertical e à derivação gástrica em Y de Roux / Analysis of the lipid profile of patients submitted to sleeve gastrectomy and Roux-en-Y gastric bypass

RESUMO Objetivo: comparar as melhorias no perfil lipídico de pacientes submetidos à gastrectomia vertical (GV) e à derivação gástrica em Y de Roux (DGYR). Metódos: estudo de coorte misto, em que foram avaliados 334 pacientes submetidos à GV e 178 pacientes submetidos à DGYR no Hospital das Clínicas da Universidade Federal de Pernambuco e no Real Hospital Português de Beneficência, Recife, PE, Brasil. Foram realizadas dosagens séricas de colesterol total, LDL, HDL e triglicerídeos no pré-operatório e com três, seis, 12 e 24 meses de seguimento. Resultados: o grupo submetido à GV foi composto por 58 homens e 276 mulheres. No grupo submetido à DGYR, foram analisados 64 homens e 114 mulheres. A média de idade foi de 37,2±20,5 anos no grupo da GV e de 41,9±11,1 anos no grupo da DGYR. O IMC médio pré-operatório foi de 39,4±2,6kg/m2 e 42,7±5,8kg/m2, para o grupo da GV e da DGYR, respectivamente. No pré-operatório, 80% dos pacientes tinha, no mínimo, uma anormalidade no perfil lipídico. Dois anos após a cirurgia houve melhora do colesterol total, LDL, HDL e triglicerídeos no grupo submetido à DGYR. No grupo submetido à GV, após dois anos houve melhora dos níveis de colesterol total, HDL e triglicerídeos, apenas. Conclusão: ambas as técnicas resultaram em melhorias no perfil lipídico, porém a DGYR foi mais efetiva.

ABSTRACT Objective: to compare the improvements in lipid profile in patients undergoing sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB). Methods: in a mixed cohort study, we evaluated 334 patients undergoing SG and 178 patients undergoing RYGB at the University Hospital of the Federal University of Pernambuco and at the Real Hospital Português de Beneficência, Recife, PE, Brazil. We measured serum levels of total cholesterol, LDL, HDL and triglycerides preoperatively and at three, six, 12 and 24 months follow-up. Results: the SG group consisted of 58 men and 276 women. In the group submitted to RYGB, there were 64 men and 114 women. The mean age was 37.2±20.5 years in the SG group and 41.9±11.1 years in the RYGB group. The preoperative mean BMI was 39.4±2.6kg/m2 and 42.7±5.8kg/m2 for the SG and RYGB groups, respectively. In the preoperative period, 80% of the patients had at least one abnormality in the lipid profile. Two years after surgery, there was improvement in total cholesterol, LDL, HDL and triglycerides in the group submitted to RYGB. In the group submitted to SG, after two years there was improvement in total cholesterol, HDL and triglyceride levels. Conclusion: both techniques resulted in improvements in the lipid profile, but the RYGB was more effective.

Modification of the natural progression of epileptogenesis by means of biperiden in the pilocarpine model of epilepsy.

Brain injuries are often associated with the later development of epilepsy. Evidence suggests that morphological and functional changes occur in the remaining neural tissue during a silent (or latent) period in which no seizures are expressed. It is believed that this silent (reorganization) period may provide a therapeutic window for modifying the natural history of disease progression. Here we provide evidence that biperiden, a muscarinic anticholinergic agent, is able to alter disease progression in an animal model of epilepsy. We observed that biperiden was capable of slowing the manifestation of the first spontaneous epileptic seizure and effectively reduced the severity and number of recurrent, spontaneous epileptic seizures during the animals' lifespan. Biomolecular (microdialysis) and electrophysiological (extracellular field recordings) studies determined that biperiden was capable of elevating the threshold of hippocampal excitability, thereby making the hippocampal glutamatergic pathways less responsive to stimuli when high concentrations of potassium were used in vivo or in vitro. Notably, there was no hindrance of long-term memory or learning (a potential problem given the amnestic nature of biperiden). We conclude that biperiden has antiepileptogenic potential and may represent an opportunity for the prevention of post-traumatic epilepsy.

Prefrontal dopamine release and sensory-specific satiety altered in rats with neonatal ventral hippocampal lesions.

Rats with a neonatal ventral hippocampal lesion (NVHL) have been used to model certain features of schizophrenia because they display dopaminergic activity and behavioral alterations consistent with a dysfunctional prefrontal cortex after puberty. Microdialysis studies in normal rats demonstrated increased prefrontal dopamine release during the incentive phase of behavior in an experimental situation specifically designed to evidence this behavioral aspect: the so called "sensory-specific satiety" procedure. Our hypothesis is that if dopaminergic activity in the prefrontal cortex of NVHL rats differs from sham lesioned rats, the responsiveness to the aforementioned experimental situation should also be different. Extracellular medial prefrontal dopamine outflow increased in hungry control rats when they had access to food and decreased across satiety. It increased again when a new food was presented, even when the rats were satiated. NVHL rats also had increased dopamine prefrontal outflow in these conditions, but it remained high after the end of the consumption period. The food consumption behavior declined less rapidly and the reinstatement of food consumption, usually produced by new food, did not occur in NVHL rats, provided the lesions were large. These data were discussed in relation to several theoretical backgrounds developed about the incentive aspect of behavior and for understanding the pathophysiology of schizophrenia.

Conditioned fear is modulated by D2 receptor pathway connecting the ventral tegmental area and basolateral amygdala.

Excitation of the mesocorticolimbic pathway, originating from dopaminergic neurons in the ventral tegmental area (VTA), may be important for the development of exaggerated fear responding. Among the forebrain regions innervated by this pathway, the amygdala is an essential component of the neural circuitry of conditioned fear. The functional role of the dopaminergic pathway connecting the VTA to the basolateral amygdala (BLA) in fear and anxiety has received little attention. In vivo microdialysis was performed to measure dopamine levels in the BLA of Wistar rats that received the dopamine D(2) agonist quinpirole (1 µg/0.2 µl) into the VTA and were subjected to a fear conditioning test using a light as the conditioned stimulus (CS). The effects of intra-BLA injections of the D(1) antagonist SCH 23390 (1 and 2 µg/0.2 µl) and D(2) antagonist sulpiride (1 and 2 µg/0.2 µl) on fear-potentiated startle (FPS) to a light-CS were also assessed. Locomotor performance was evaluated by use of open-field and rotarod tests. Freezing and increased dopamine levels in the BLA in response to the CS were both inhibited by intra-VTA quinpirole. Whereas intra-BLA SCH 23390 did not affect FPS, intra-BLA sulpiride (2 µg) inhibited FPS. Sulpiride's ability to decrease FPS cannot be attributed to nonspecific effects because this drug did not affect motor performance. These findings indicate that the dopamine D(2) receptor pathway connecting the ventral tegmental area and the basolateral amygdala modulates fear and anxiety and may be a novel pharmacological target for the treatment of anxiety.

Acoustic hypersensitivity in adult rats after neonatal ventral hippocampus lesions.

Rats with a bilateral neonatal ventral hippocampus lesion (NVHL) are used as models of neurobiological aspects of schizophrenia. In view of their decreased number of GABAergic interneurons, we hypothesized that they would show increased reactivity to acoustic stimuli. We systematically characterized the acoustic reactivity of NVHL rats and sham operated controls. They were behaviourally observed during a loud white noise. A first cohort of 7 months' old rats was studied. Then the observations were reproduced in a second cohort of the same age after characterizing the reactivity of the same rats to dopaminergic drugs. A third cohort of rats was studied at 2, 3, 4, 5 and 6 months. In subsets of lesioned and control rats, inferior colliculus auditory evoked potentials were recorded. A significant proportion of rats (50-62%) showed aberrant audiogenic responses with explosive wild running resembling the initial phase of audiogenic seizures. This was not correlated with their well-known enhanced reactivity to dopaminergic drugs. The proportion of rats showing this strong reaction increased with rats' age. After the cessation of the noise, NVHL rats showed a long freezing period that did neither depend on the size of the lesion nor on the rats' age. The initial negative deflection of the auditory evoked potential was enhanced in the inferior colliculus of only NVHL rats that displayed wild running. Complementary anatomical investigations using X-ray scans in the living animal, and alizarin red staining of brain slices, revealed a thin layer of calcium deposit close to the medial geniculate nuclei in post-NVHL rats, raising the possibility that this may contribute to the hyper-reactivity to sounds seen in these animals. The findings of this study provide complementary information with potential relevance for the hyper-reactivity noted in patients with schizophrenia, and therefore a tool to investigate the underlying biology of this endophenotype.

Involvement of median raphe nucleus 5-HT1A receptors in the regulation of generalized anxiety-related defensive behaviours in rats.

Changes in 5-HT1A receptor-mediated neurotransmission at the level of the median raphe nucleus (MRN) are reported to affect the expression of defensive responses that are associated with generalized anxiety disorder (e.g. inhibitory avoidance) but not with panic (e.g. escape). The objective of this study was to further explore the involvement of MRN 5-HT1A receptors in the regulation of generalized anxiety-related behaviours. Results of experiment 1 showed that intra-MRN injection of the 5-HT1A/7 receptor agonist 8-OH-DPAT (0.6 nmol) in male Wistar rats impaired the acquisition of inhibitory avoidance, without interfering with the performance of escape in the elevated T-maze test of anxiety. Pre-treatment with the 5-HT1A receptor antagonist WAY-100635 (0.18 nmol) fully blocked this anxiolytic-like effect. As revealed by experiment 2, intra-MRN injection of 8-OH-DPAT (0.6, 3 or 15 nmol) also caused anxiolytic effect in rats submitted to the light-dark transition test, another animal model that has been associated with generalized anxiety. In the same test, intra-MRN injection of WAY-100635 (0.18, 0.37 or 0.74 nmol) caused the opposite effect. Overall, the current findings support the view that MRN 5-HT neurons, through the regulation of 5-HT1A somatodendritic autoreceptors, are implicated in the regulation of generalized anxiety-associated behaviours.

Overshadowing in conditioned taste aversion or in conditioned emotional response after neonatal ventral hippocampal lesions in rats.

The neonatal hippocampus lesion thought to model schizophrenia should show the same modifications in behavioural tests as other models, especially pharmacological models, namely decreased latent inhibition, blocking and overshadowing. The present study is set out to evaluate overshadowing in order to complement our previous studies, which had tested latent inhibition. "Overshadowing" refers to the decreased conditioning that occurs when the to-be-conditioned stimulus is combined with another stimulus at the conditioning stage. We used the same two Pavlovian conditioning paradigms as in our previous works, namely conditioned taste aversion (CTA) and conditioned emotional response (CER). A sweet taste overshadowed a salty conditioned stimulus, and a tone overshadowed a flashing light. Totally different stimuli were used to counter possible sensory biases. The protocols were validated with two groups of Sprague Dawley rats. The same two protocols were then applied to a cohort of rats whose ventral hippocampus had been destroyed when they were 7days old. Only rats with extended ventral hippocampus lesions were included. The overall effect of Pavlovian conditioning was attenuated, significantly so in the conditioned emotional response paradigm, but overshadowing appeared not to be modified in either the conditioned emotional response or the conditioned taste aversion paradigm.

Rewarded associative and instrumental conditioning after neonatal ventral hippocampus lesions in rats.

Sprague Dawley rats were submitted to bilateral ventral hippocampus lesions 7 days after birth. This corresponds to the Lipska and Weinberger's procedure for modeling schizophrenia. The aim of the present work was to test the learning capacity of such rats with an associative Pavlovian and an instrumental learning paradigm, both methods using reward outcome (food, sucrose or polycose). The associative paradigm comprised also a second learning test with reversed learning contingencies. The instrumental conditioning comprised an extinction test under outcome devaluation conditions. Neonatally lesioned rats, once adults (over 60 days of age), showed a conditioning deficit in the associative paradigm but not in the instrumental one. Lesioned rats remained able to adapt as readily as controls to the reversed learning contingency and were as sensitive as controls to the devaluation of outcome. Such observations indicate that the active access (instrumental learning) to a reward could have compensated for the deficit observed under the "passive" stimulus-reward associative learning condition. This feature is compared to the memory management impairments observed in clinical patients.

Alteration of conditioned emotional response and conditioned taste aversion after neonatal ventral hippocampus lesions in rats.

Sprague-Dawley rats were submitted to bilateral ventral hippocampus lesions 7 days after birth according to the Lipska and Weinberger's procedure for modeling schizophrenia. The aim of the present work was to better characterize their learning capacity. A double latent inhibition study was conducted using respectively conditioned taste aversion and conditioned emotional response. In the background of this evaluation, locomotion under apomorphine and startle reactions, inhibited or not by prepulses, was also evaluated. Our experimental methods were the same as those used in previous studies from the laboratory which were found to be sensitive to pharmacological manipulations and shown by others to be unaffected by lesions of the ventral hippocampus carried out in adult rats. In contrast, neonatally lesioned rats, once adults (over 60 days old), were hyper-responsive to noise--i.e., the startle response to a 105 db(A) noise pulse was enhanced--and hyperactive under apomorphine (0.7 mg/kg). The prepulse inhibition properties of the startle remained unchanged. Lesioned rats showed a deficit but not a suppression of conditioning, similar in both tests, but latent inhibition was preserved. Such observations complement the already known memory deficit produced in this neurodevelopmental model of schizophrenia.

5-HT2 receptor mechanisms of the dorsal periaqueductal gray in the conditioned and unconditioned fear in rats.

RATIONALE: It is well known that 5-HT(2) mechanisms modulate the defensive behavior produced by the stimulation of the dorsal periaqueductal gray (dPAG). However, in spite of the notion that past stressful experiences play a role in certain types of anxiety, only studies with the stimulation of the dPAG of rats without previous aversive experience have been conducted so far. OBJECTIVES: We investigated the mediation of 5-HT(2) receptors of the dPAG in rats previously submitted to contextual fear conditioning (CFC). Defensive behaviors induced by the activation of the dPAG were assessed by measuring the lowest intensity of electric current applied to this structure (threshold) able to produce freezing and escape responses during the testing sessions of CFC in which animals were placed in a context previously paired to footshocks. The 5-HT(2) function of the dPAG in this condition was evaluated by local injections of alpha-methyl-5-HT (20 nmol/0.2 mul) and ketanserin (5 and 10 nmol/0.2 mul), selective agonist and antagonist of 5-HT(2) receptors, respectively. RESULTS: In accordance with previous studies, alpha-methyl-5-HT increased the aversive thresholds (antiaversive effects) in naive rats, and injection of ketanserin into the dPAG did not produce significant effects. On the other hand, ketanserin decreased in a dose-dependent manner the freezing threshold (proaversive effect) determined by the dPAG electrical stimulation, whereas alpha-methyl-5-HT continued to show antiaversive effects in animals under CFC. CONCLUSIONS: The present results suggest that past stressful experience can produce changes in the synaptic function of 5-HT(2) receptors within the dPAG with important impact on the expression of defensive behaviors.

5-HT2- and D1-mechanisms of the basolateral nucleus of the amygdala enhance conditioned fear and impair unconditioned fear.

The inferior colliculus (IC) is involved in processing of auditory information, but also integrates acoustic information of aversive nature. In fact, chemical stimulation of the IC with semicarbazide (SMC) - an inhibitor of the GABA synthesizing enzyme glutamic acid decarboxylase - has been found to cause defensive behavior in an open-field test and functions as an unconditioned stimulus in the place conditioned aversion test (PCA). A question has arisen regarding whether the basolateral nucleus of the amygdala (BLA) is involved in the acquisition of the aversive information ascending from the IC and whether dopaminergic and serotoninergic mechanisms of the BLA regulate this process. Recent evidence has shown that inactivation of the BLA with muscimol inhibits the PCA and causes an increase in the aversiveness of the chemical stimulation of the IC. Based on this, we examined the effects of ketanserin and SCH-23390, antagonists of the 5HT(2) and D(1) receptors, respectively, on the conditioned and unconditioned fear elicited by IC stimulation with SMC. The results obtained confirm the crucial role of 5-HT(2)- and D(1)-mechanisms of the BLA on conditioned fear in that ketanserin and SCH-23390 injections into the BLA caused a reduction in the PCA. On the other hand, ketanserin and SCH-23390 injections into the BLA enhanced the aversiveness of the IC injections of SMC. These findings suggest that while 5-HT(2) and DA(1) mechanisms in the BLA appear to facilitate the conditioned fear they inhibit the unconditioned fear triggered by IC activation.

Conditioned and unconditioned fear organized in the inferior colliculus are differentially sensitive to injections of muscimol into the basolateral nucleus of the amygdala.

Chemical stimulation of the inferior colliculus (IC) with semicarbazide--an inhibitor of the gamma aminobutyric acid synthesizing enzyme--functions as an unconditioned stimulus in the conditioned place aversion test (CPA), and electrolytic lesions of the basolateral amygdala (BLA) enhance the aversiveness of the IC stimulation. This study examined the effects of inactivation of the BLA with muscimol on the conditioned and unconditioned fear using semicarbazide injections into the IC of rats subjected to conditioned (CPA) or unconditioned (open field) fear tests. In both tests, the rats were injected with semicarbazide or saline into the IC and muscimol or saline into the BLA. Muscimol decreased the CPA and increased the unconditioned fear elicited by IC injections of semicarbazide. These findings indicate that distinct modulatory mechanisms in the BLA are recruited during the conditioned and unconditioned fear triggered by IC activation.

Pharmacological assessment of the freezing, antinociception, and exploratory behavior organized in the ventrolateral periaqueductal gray.

Opioid and serotonergic mechanisms of the ventrolateral periaqueductal gray (vlPAG) are recruited by conditioned freezing and antinociception. However, it is unclear whether freezing and antinociception induced by stimulation of the vlPAG are interrelated. To address this issue we looked at the effects of the opioid antagonist naltrexone, the 5-HT2 antagonist ketanserin, and the benzodiazepine agonist midazolam injected into the vlPAG on the freezing and antinociception induced by electrical stimulation of this region. This antinociception was evaluated by the tail-flick and formalin tests. To further characterize the involvement of the vlPAG in unconditioned fear, the effects of intra-vlPAG injections of midazolam on the exploratory behavior were also assessed in independent groups of rats submitted to the elevated plus-maze test (EPM). The data obtained showed that: (i) electrical stimulation of the vlPAG causes freezing blocked by midazolam but not by naltrexone and ketanserin; (ii) antinociception generated at the level of the vlPAG is inhibited by naltrexone, ketanserin, and midazolam; (iii) activation of benzodiazepine-mediated mechanisms in the vlPAG increased the exploratory behavior of rats in the closed arms but not the avoidance behavior of open arms of the EPM. Thus, freezing and antinociception generated in the vlPAG are dissociated pharmacologically. Whereas antinociception is a multimediated process sensitive to naltrexone, ketanserin, and midazolam, the freezing induced by vlPAG stimulation was reversed only by the benzodiazepine compound. As injections of midazolam into the vlPAG do not cause anxiolytic effects in the EPM, the aversive stimuli inherent of this test seem to bypass the vlPAG.

Behavioral effects of systemically administered MK-212 are prevented by ritanserin microinfusion into the basolateral amygdala of rats exposed to the elevated plus-maze.

RATIONALE: Although 5-HT2 receptors seem to play an important role in anxiety, results from numerous studies are still highly variable. Moreover, little is known about the behavioral effects of centrally administered 5-HT2 compounds in animal models of anxiety. OBJECTIVE: The current study was performed to: (1) further investigate the effects of 5-HT2 receptor activation in rats exposed to the elevated plus-maze (EPM) and the open-field arena, two widely used animal models for studying anxiety and locomotor activity; and (2) evaluate the involvement of the 5-HT2 receptors within the basolateral nucleus of the amygdala (BLA) in the modulation of such effects. METHODS: In the first experiment, male Wistar rats were exposed for 5 min to the EPM 27 min following intraperitoneal (i.p.) (1.0 ml/kg) injections of the preferential 5-HT2C receptor agonist 6-chloro-2[1-piperazinyl]pyrazine (MK-212) at doses of 1.0, 2.0, or 4.0 mg/kg. Control animals were injected with saline. The percentage of open-arm entries and the percentage of time spent in these arms were employed as anxiety indexes, whereas the number of closed-arm entries was calculated as indicative of locomotor activity. In the second experiment, rats were exposed for 10 min in an open-field arena to further assess the interference of the same MK-212 doses upon locomotor activity. In Experiment 3, rats were microinjected (0.2 microl) either with the mixed 5-HT 2A/2C receptor antagonist ritanserin (0.5, 1.25, 2.5, and 5.0 microg) or its vehicle into the BLA 12 min following i.p. injections of saline or the intermediate dose of MK-212 (2.0 mg/kg). Fifteen minutes later, each animal was exposed to the EPM as before. RESULTS: Whereas the highest dose of MK-212 (4.0 mg/kg) induced motor-suppressant effects in both EPM and open-field arena, the intermediate dose of the drug (2.0 mg/kg) reduced open-arm exploration without significantly affecting the number of closed-arm entries. This behavioral profile, consistent with selective anxiogenic effect in the EPM, was dose-dependently prevented by ritanserin microinfusion into the BLA. In saline-pretreated animals, however, ritanserin (all doses) was ineffective. CONCLUSIONS: MK-212 increases anxiety and decreases locomotor activity. The anxiogenic-like profile of 5-HT2 receptor activation is prevented by the blockade of 5-HT2 receptors within the BLA, which does not have an effect by itself upon basal anxiety levels triggered by the EPM.