Summating Potential as Marker of Intracochlear Position in Bipolar Electrocochleography.

OBJECTIVES: Cochlear implantation criteria include subjects with residual low-frequency hearing. To minimize implantation trauma and to avoid unwanted interactions of electric- and acoustic stimuli, it is often recommended to stop cochlear implantation before the cochlear implant (CI) reaches the cochlear partition with residual hearing, as determined by an audiogram. For this purpose, the implant can be used to record acoustically evoked signals during implantation, including cochlear compound action potentials (CAP), cochlear microphonics (CMs), and summating potentials (SPs). The former two have previously been used to monitor residual hearing in clinical settings. DESIGN: In the present study we investigated the use of intracochlear, bipolar SP recordings to determine the exact cochlear position of the contacts of implanted CIs in guinea pig cochleae (n = 13). Polarity reversals of SPs were used as a functional marker of intracochlear position. Micro computed tomography (µCT) imaging and a modified Greenwood function were used to determine the cochleotopic positions of the contacts in the cochlea. These anatomical reconstructions were used to validate the SP-based position estimates. RESULTS: The precision of the SP-based position estimation was on average within ± 0.37 octaves and was not impaired by moderate hearing loss caused by noise exposure after implantation. It is important to note that acute hearing impairment did not reduce the precision of the method. The cochleotopic position of CI accounted for ~70% of the variability of SP polarity reversals. Outliers in the dataset were associated with lateral CI positions. Last, we propose a simplified method to avoid implantation in functioning parts of the cochlea by approaching a predefined frequency region using bipolar SP recordings through a CI. CONCLUSIONS: Bipolar SP recordings provide reliable information on electrode position in the cochlea. The position estimate remains reliable after moderate hearing loss. The technique presented here could be applied during CI surgery to monitor the CI approach to a predefined frequency region.

The impact of mTOR inhibitors in the regression of left ventricular hypertrophy in elderly kidney transplant recipients.

End-stage kidney disease is frequently associated with left ventricular hypertrophy (LVH), a condition more prevalent in the elderly, that may increase mortality after renal transplantation (RTx). Previous studies suggested that mTOR inhibitors (mTORi) can improve LVH, but this has never been tested in elderly kidney transplant recipients. In this prospective randomized clinical trial, we analyzed the impact of Everolimus (EVL) on the reversal of LVH after RTx in elderly recipients (≥60 years) submitted to different immunosuppressive regimens: EVL/lowTacrolimus (EVL group, n = 53) or mycophenolate sodium/regularTacrolimus (MPS group, n = 47). Patients performed echocardiograms (Echo) up to 3 months after RTx and then annually. At baseline, mean age was 65±3 years in both groups and LVH was observed in 63.6% of patients in EVL group and in 61.8% of MPS group. Last Echo was performed at mean time of 47 and 49 months after RTx in EVL and MPS groups, respectively (P = .34). LVH regression was observed in 23.8% (EVL group) and 19% (MPS group) of patients (P = 1.00). Mean eGFR, blood pressure, and use of RAS blockers were similar between groups throughout follow-up. EVL did not improve LVH in this cohort, and this lack of benefit may be attributed to concomitant use of TAC, senescence, or both.

Repeated crack cocaine administration alters panic-related responses and delta FosB immunoreactivity in panic-modulating brain regions.

Crack cocaine is the crystal form of cocaine, produced by adding sodium bicarbonate to cocaine base paste. Brazil is the largest consumer of crack cocaine in the world. Users of crack cocaine show important physiological and behavioral alterations, including neuropsychiatric symptoms, such as anxiety-related symptoms. Nevertheless, few pre-clinical studies have been previously performed to understand the neurobiological effects of crack cocaine. The purpose of the present study was to investigate effects of the subchronic treatment (5 days, IP) of rats with crack cocaine in an animal model of anxiety/panic, the elevated T-maze (ETM). The ETM model allows the measurement of two behavioral defensive responses, avoidance and escape, in clinical terms, respectively, associated to generalized anxiety and panic disorder, the two main psychiatric conditions that accompany substance use disorders. Immediately after the ETM model, animals were tested in an open field for locomotor activity assessment. Analysis of delta FosB protein immunoreactivity was used to map areas activated by crack cocaine exposure. Results showed that crack treatment selectively altered escape displayed by rats in the ETM test, inducing either a panicolytic (18 mg/kg IP) or a panicogenic-like effect (25 and 36 mg/kg IP). These effects were followed by the altered functioning of panic-modulating brain regions, i.e., the periaqueductal gray and the dorsal region and lateral wings of the dorsal raphe nucleus. Treatment with 36 mg/kg of crack cocaine also increased locomotor activity. These are the first observations performed with crack cocaine in a rodent model of anxiety/panic and contribute to a better understanding of the behavioral and neurobiological effects of crack cocaine.

Higher-order dispersion and the spectral behavior in a doubly resonant optical parametric oscillator.

In doubly resonant optical parametric oscillators (DROPOs), it is possible to generate, enhance, and phase lock two frequencies at once. Following intracavity phase conditions, a complex tuning behavior of the signal and idler spectra takes place in DROPOs, cumulating into degeneracy with phase self-locking and coherent wavelength doubling. In this work, we identify group delay matching as the important parameter determining the global tuning behavior and demonstrate the key role of higher-order dispersion in the spectral dependencies. Applicationwise, we suggest a simple way to control the phase self-locking region by varying the intracavity third-order dispersion.

Lactulose decreases neuronal activation and attenuates motor behavioral deficits in hyperammonemic rats.

Lactulose is a nonabsorbable disaccharide commonly used in clinical practice to treat hepatic encephalopathy. However, its effects on neuropsychiatric disorders and motor behavior have not been fully elucidated. Male Wistar rats were bile-duct ligated, and 3 weeks after surgery, treated with lactulose administrated by gavage (1.43 or 3.57 g/kg), once a day for seven days. Plasma levels of ammonia, aspartate aminotransferase, total bilirubin, and creatinine were quantified and histopathological analysis of the livers was performed. Locomotor activity measurements were performed in an open field. The expression of water channel aquaporin-4 was investigated and the analysis of Fos protein immunoreactivity was used to evaluate the pattern of neural activation in brain areas related to motor behavior. Bile-duct ligated rats showed hyperammonemia, loss of liver integrity and function, impaired locomotor activity, reduced aquaporin-4 protein expression, and neuronal hyperactivity. Lactulose treatment was able to reduce ammonia plasma levels, despite not having an effect on biochemical parameters of liver function, such as aspartate aminotransferase activity and total bilirubin levels, or on the cirrhotic hepatic architecture. Lactulose was also able to reduce the locomotor activity impairments and to mitigate or reverse most changes in neuronal activation. Lactulose had no effect on reduced aquaporin-4 protein expression. Our findings confirm the effectiveness of lactulose in reducing hyperammonemia and neuronal hyperactivity in brain areas related to motor behavior, reinforcing the importance of its clinical use in the treatment of the symptoms of cirrhosis-associated encephalopathy.

Short-term outcomes after selective shunt during carotid endarterectomy: a propensity score matching analysis.

INTRODUCTION AND OBJECTIVES: Carotid cross-clamping during carotid endarterectomy might lead to intraoperative neurologic deficits, increasing stroke/death risk. If deficits are detected, carotid shunting has been recommended to reduce the risk of stroke. However, shunting may sustain a specific chance of embolic events and subsequently incurring harm. Current evidence is still questionable regarding its clear benefit. The aim is to determine whether a policy of selective shunt impacts the complication rate following an endarterectomy. MATERIAL AND METHODS: From January 2013 to May 2021, all patients undergoing carotid endarterectomy under regional anesthesia with intraoperative neurologic alteration were retrieved. Patients submitted to selective shunt were compared to a non-shunt group. A 1:1 propensity score matching (PSM) was performed. Differences between the groups and clinical outcomes were calculated, resorting to univariate analysis. RESULTS: Ninety-eight patients were selected, from which 23 were operated on using a shunt. After PSM, 22 non-shunt patients were compared to 22 matched shunted patients. Concerning demographics and comorbidities, both groups were comparable to pre and post-PSM, except for chronic heart failure, which was more prevalent in shunted patients (26.1%, P=0.036) in pre-PSM analysis. Regarding 30-day stroke and score Clavien-Dindo ≥2, no significant association was found (P=0.730, P=0.635 and P=0.942, P=0.472, correspondingly, for pre and post-PSM). CONCLUSIONS: In this cohort, resorting to shunting did not demonstrate an advantage regarding 30-day stroke or a Clavien-Dindo ≥ 2 rates. Nevertheless, additional more extensive studies are mandatory to achieve precise results concerning the accurate utility of carotid shunting in this subset of patients under regional anesthesia.

Neuroprotective effects of platinum nanoparticle-based microreactors in bicuculline-induced seizures.

Epilepsy designates a group of chronic brain disorders, characterized by the recurrence of hypersynchronous, repetitive activity, of neuronal clusters. Epileptic seizures are the hallmark of epilepsy. The primary goal of epilepsy treatment is to eliminate seizures with minimal side effects. Nevertheless, approximately 30% of patients do not respond to the available drugs. An imbalance between excitatory/inhibitory neurotransmission, that leads to excitotoxicity, seizures, and cell death, has been proposed as an important mechanism regarding epileptogenesis. Recently, it has been shown that microreactors composed of platinum nanoparticles (Pt-NP) and glutamate dehydrogenase possess in vitro and in vivo activity against excitotoxicity. This study investigates the in vivo effects of these microreactors in an animal model of epilepsy induced by the administration of the GABAergic antagonist bicuculline. Male Wistar rats were administered intracerebroventricularly (i.c.v.) with the microreactors or saline and, five days later, injected with bicuculline or saline. Seizure severity was evaluated in an open field. Thirty min after behavioral measurements, animals were euthanized, and their brains processed for neurodegeneration evaluation and for neurogenesis. Treatment with the microreactors significantly increased the time taken for the onset of seizures and for the first tonic-clonic seizure, when compared to the bicuculline group that did not receive the microreactor. The administration of the microreactors also increased the time spent in total exploration and grooming. Treatment with the microreactors decreased bicuculline-induced neurodegeneration and increased neurogenesis in the dorsal and ventral hippocampus. These observations suggest that treatment with Pt-NP-based microreactors attenuates the behavioral and neurobiological consequences of epileptiform seizure activity.

Voltammetric determination of cocaine in confiscated samples using a carbon paste electrode modified with different [UO2(X-MeOsalen)(H2O)] · H2O complexes.

A fast and non-destructive voltammetric method to detect cocaine in confiscated samples based on carbon paste electrode modified with methoxy-substituted N,N'-ethylene-bis(salcylideneiminato)uranyl(VI)complexes, [UO2(X-MeOSalen)(H2O)] · H2O, where X corresponds to the positions 3, 4 or 5 of the methoxy group on the aromatic ring, is described. The electrochemical behavior of the modified electrode and the electrochemical detection of cocaine were investigated using cyclic voltammetry. Using 0.1 mol · L(-1) KCl as supporting-electrolyte, a concentration-dependent, well-defined peak current for cocaine at 0.62 V, with an amperometric sensitivity of 6.25 × 104 µA · mol · L(-1) for cocaine concentrations ranging between 1.0 × 10(-7) and 1.3 × 10(-6) mol · L-1 was obtained. Chemical interference studies using lidocaine and procaine were performed. The position of the methoxy group affects the results, with the 3-methoxy derivative being the most sensitive.

Prepulse inhibition of the acoustic startle reflex impairment by 5-HT2A receptor activation in the inferior colliculus is prevented by GABAA receptor blockade in the pedunculopontine tegmental nucleus.

The relationship between serotonin dysfunction and schizophrenia commenced with the discovery of the effects of lysergic acid diethylamide (LSD) that has high affinity for 5-HT2A receptors. Activation of these receptors produces perceptual and behavioural changes such as illusions, visual hallucinations and locomotor hyperactivity. Using prepulse inhibition (PPI) of the acoustic startle, which is impaired in schizophrenia,we aimed to investigate:i) the existence of a direct and potentially inhibitory neural pathway between the inferior colliculus (IC) and the pedunculopontine tegmental nucleus (PPTg) involved in the mediation of PPI responses by a neural tract tracing procedure;ii) if the microinjection of the 5-HT2A receptors agonist DOI in IC would activate neurons in this structure and in the PPTg by a c-Fos protein immunohistochemistry study;iii) whether the deficits in PPI responses, observed after the administration of DOI in the IC, could be prevented by the concomitant microinjection of the GABAA receptor antagonist bicuculline in the PPTg.Male Wistar rats were used in this study. An IC-PPTg reciprocated neuronal pathway was identified by neurotracing. The number of c-Fos labelled cells was lower in the DOI group in IC and PPTg, suggesting that this decrease could be due to the high levels of GABA in both structures. The concomitant microinjections of bicuculline in PPTg and DOI in IC prevented the PPI deficit observed after the IC microinjection of DOI. Our findings suggest that IC 5-HT2A receptors may be at least partially involved in the regulation of inhibitory pathways mediating PPI response in IC and PPTg structures.

Stability of dental implants after irradiation with an 830-nm low-level laser: a double-blind randomized clinical study.

Little is known about the benefits of low-level laser therapy (LLLT) on improvement of stability of dental implants. The aim of this randomized clinical study was to assess the LLLT effect on implants stability by means of resonance frequency analysis (RFA). Thirty implants were distributed bilaterally in the posterior mandible of eight patients. At the experimental side, the implants were submitted to LLLT (830 nm, 86 mW, 92.1 J/cm(2), 0.25 J, 3 s/point, at 20 points), and on the control side, the irradiation was simulated (placebo). The first irradiation was performed in the immediate postoperative period, and it was repeated every 48 h in the first 14 days. The initial implant stability quotient (ISQ) of the implants was measured by means of RFA. New ISQ measurements were made after 10 days, 3, 6, 9, and 12 weeks. The initial ISQ values ranged from 65-84, with a mean of 76, undergoing a significant drop in stability from the 10th day to the 6th week in the irradiated group, and presenting a gradual increase from the 6th to the 12th week. The highest ISQ values were observed on the 10th day in the irradiated group, and the lowest in the 6th week in both groups. Under the conditions of this study, no evidence was found of any effect of LLLT on the stability of the implants when measured by RFA. Since high primary stability and good bone quality are of major relevancy for a rigid bone-implant interface, additional LLLT may have little impact macroscopically.

Platinum nanoparticle-based microreactors protect against the behavioral and neurobiological consequences of chronic stress exposure.

Excitotoxicity is described as the exacerbated activation of glutamate AMPA and NMDA receptors that leads to neuronal damage, and ultimately to cell death. Astrocytes are responsible for the clearance of 80-90% of synaptically released glutamate, preventing excitotoxicity. Chronic stress renders neurons vulnerable to excitotoxicity and has been associated to neuropsychiatric disorders, i.e., anxiety. Microreactors containing platinum nanoparticles (Pt-NP) and glutamate dehydrogenase have shown in vitro activity against excitotoxicity. The purpose of the present study was to investigate the in vivo effects of these microreactors on the behavioral and neurobiological effects of chronic stress exposure. Rats were either unstressed or exposed for 2 weeks to an unpredictable chronic mild stress paradigm (UCMS), administered intra-ventral hippocampus with the microreactors (with or without the blockage of astrocyte functioning), and seven days later tested in the elevated T-maze (ETM; Experiment 1). The ETM allows the measurement of two defensive responses, avoidance and escape, in terms of psychopathology respectively related to generalized anxiety and panic disorder. Locomotor activity in an open field was also measured. Since previous evidence shows that stress inhibits adult neurogenesis, we evaluated the effects of the different treatments on the number of cells expressing the marker of migrating neuroblasts doublecortin (DCX) in the dorsal and ventral hippocampus (Experiment 2). Results showed that UCMS induces anxiogenic effects, increases locomotion, and decreases the number of DCX cells in the dorsal and ventral hippocampus, effects that were counteracted by microreactor administration. This is the first study to demonstrate the in vivo efficacy of Pt-NP against the behavioral and neurobiological effects of chronic stress exposure.

Clozapine prevented social interaction deficits and reduced c-Fos immunoreactivity expression in several brain areas of rats exposed to acute restraint stress.

In the present study, we evaluate the effect of acute restraint stress (15 min) of male Wistar rats on social interaction measurements and c-Fos immunoreactivity (c-Fos-ir) expression, a marker of neuronal activity, in areas involved with the modulation of acute physical restraint in rats, i.e., the paraventricular nucleus of the hypothalamus (PVN), median raphe nucleus (MnR), medial prefrontal cortex (mPFC), cingulate prefrontal cortex (cPFC), nucleus accumbens (NaC), hippocampus (CA3), lateral septum (LS) and medial amygdala (MeA). We considered the hypothesis that restraint stress exposure could promote social withdrawal induced by the activation of the hypothalamic-pituitary-adrenocortical (HPA) axis, and increase c-Fos expression in these limbic forebrain areas investigated. In addition, we investigated whether pretreatment with the atypical antipsychotic clozapine (5 mg/kg; I.P.) could attenuate or block the effects of restraint on these responses. We found that restraint stress induced social withdrawal, and increased c-Fos-ir in these areas, demonstrating that a single 15 min session of physical restraint of rats effectively activated the HPA axis, representing an effective tool for the investigation of neuronal activity in brain regions sensitive to stress. Conversely, pretreatment with clozapine, prevented social withdrawal and reduced c-Fos expression. We suggest that treatment with clozapine exerted a preventive effect in the social interaction deficit, at least in part, by blocking the effect of restraint stress in brain regions that are known to regulate the HPA-axis, including the cerebral cortex, hippocampus, hypothalamus, septum and amygdala. Further experiments will be done to confirm this hypothesis.

Human mucosal leishmaniasis: neutrophils infiltrate areas of tissue damage that express high levels of Th17-related cytokines.

Mucosal leishmaniasis (ML) is characterised by severe tissue destruction. Herein, we evaluated the involvement of the IL-17-type response in the inflammatory infiltrate of biopsy specimens from 17 ML patients. IL-17 and IL-17-inducing cytokines (IL-1ß, IL-23, IL-6 and TGF-ß) were detected by immunohistochemistry in ML patients. IL-17(+) cells exhibited CD4(+), CD8(+) or CD14(+) phenotypes, and numerous IL-17(+) cells co-expressed the CC chemokine receptor 6 (CCR6). Neutrophils, a hallmark of Th17-mediated inflammation, were regularly detected in necrotic and perinecrotic areas and stained positive for neutrophil elastase, myeloperoxidase and MMP-9. Taken together, these observations demonstrate the existence of Th17 cells in ML lesions associated with neutrophils in areas of tissue injury and suggest that IL-17 is involved in ML pathogenesis.

Role of contrast-enhanced transesophageal echocardiography for detection of and scoring intrapulmonary vascular dilatation.

BACKGROUND: Intrapulmonary vascular dilatations (IVD) are microvascular pulmonary changes mediated by nitric oxide that cause right-to-left shunt and hypoxemia. Contrast-enhanced transthoracic echocardiography (cTTE) is the gold standard diagnostic test for IVD. OBJECTIVE: To evaluate contrast-enhanced transesophageal echocardiography (cTEE) in the diagnosis and grading of IVD. METHODS: A study group (SG) of 63 cirrhotic patients were compared to 20 shunt-free control subjects (CG). Both groups underwent cTEE and cTTE using intravenous injections of agitated saline solution for contrast tests. Patients with patent foramen ovale, when detected, were excluded. Late appearance of microbubbles in the left atrium was diagnostic of pulmonary shunt (positive contrast test) and was graded as trivial, mild, moderate or severe by cTEE. Contrast tests were negative in 7 patients (35%) and trivial in the remaining 13 (65%) in CG, so only contrast grades ≥ mild were considered to be positive IVD tests in the SG. Gasometric change was expressed as the alveolar-arterial oxygen tension difference (A-aO2D) and was considered abnormally high at values >20 mmHg. RESULTS: SG: positive IVD tests were present in 23 patients (36%) by cTTE and 47 (75%) by cTEE (P < 0.001). These patients showed A-aO2D values significantly higher than those with negative IVD tests (P < 0.02) and were directly proportional to the contrast grade. cTEE allowed the diagnosis of IVD in three additional patients with high A-aO2D that were not detected by cTTE. CONCLUSION: cTEE enabled diagnosis of IVD in a greater number of patients with gasometric changes compared to cTTE. The contrast effect grade by cTEE seems to be proportional to IVD magnitude.

Schistosoma mansoni: an unusual cause of ovarian pseudotumor.

BACKGROUND: Schistosomiasis is a disease prevalent throughout the world, but the involvement of ovary by Schistosoma mansoni eggs is rarely found. The pathological mechanisms involved in the infestation of the ovary remain unknown and the diagnosis usually occurs, retrospectively, by histopathological examination. An uncommon case of ovarian pseudotumor due to Manson's schistosomiasis is reported. CASE: A 40-year-old woman referred with recurrent poorly characterized pelvic pain underwent surgical exploration and right salpingo-oophorectomy to treat a mixed cystic and solid ovarian tumor demonstrated preoperatively by transvaginal ultrasound of pelvis. The pathological examination of surgical product revealed a pseudotumor due to granulomatous reaction triggered by eggs of S. mansoni. The patient was referred to clinical treatment with oxamniquine and remained asymptomatic for a year follow-up. CONCLUSIONS: Ovarian ectopic S. mansoni is rarely reported in the most current literature; however, this actual proportion of ovarian Manson's schistosomiasis may not represent the real female genital involvement rates and reflect an underestimation of internal genital disease.

Exercise echocardiography in cryopreserved aortic homografts: comparison of a prototype stentless, a stented bioprosthesis, and native aortic valves.

BACKGROUND: Aortic valve replacement with a cryopreserved aortic homograft (CH) is an attractive alternative to bioprosthesis implantation. The aim of the study was to compare the hemodynamic performance of CH implanted with aortic root inclusion compared to prototype stentless (SS) bioprosthesis, standard stented (SD) bioprosthesis, and a native aortic valve. METHODS: Hemodynamics and Doppler echocardiographic measurements such as left ventricular ejection fraction, aortic valve orifice area index (AVOAI), mean and maximal transvalvular gradients, were obtained at rest and immediately after exercise in 28 patients after aortic valve replacement with CH (n = 10), SS (n = 9), or SD (n = 9), and in a control group (CG) of 15 normal volunteers. RESULTS: Rest and peak exercise heart rate and workload achieved were not different among the groups. Baseline AVOAI was larger for CH and CG compared to SS and SD groups (P < 0.05). Maximal and mean transvalvular pressure gradients at rest were lower for CH compared to SS and SD groups (P < 0.05), but higher than CG (P < 0,05). CONCLUSION: Implanted aortic CH had better hemodynamic performance than SS and SD bioprosthesis and similar to native normal aortic valves, both at rest and immediately after exercise.

Chronic corticosterone increases ΔFOSB and CRFR1 immunoreactivity in brain regions that modulate aversive conditioning.

Previous studies showed that chronic treatment with corticosterone facilitates elevated T-maze (ETM) inhibitory avoidance and a step-down avoidance task, responses that have been used to investigate aversive conditioning and memory processes. On the other hand, chronic corticosterone does not alter ETM escape from the open arms. The purpose of the present study was to further investigate the effects of chronic corticosterone treatment (200 mg pellets, 21-day release) in an animal model of anxiety that does not involve aversive conditioning: the light/dark transition model. We also investigated the pattern of ΔFosB immunoreactivity (ΔFosB-ir) in different brain regions. To examine how treatment with chronic corticosterone interferes with CRFR1 expression we measured CRFR1 in the same brain structures that exhibited increased ΔFosB-ir. Results showed that chronic treatment with corticosterone did not alter behavioral measurements performed in the light/dark transition model. On the other hand, ΔFosB-ir was increased in several structures that modulate aversive conditioning: the cingulate cortex, the ventro and dorsolateral septum, the amygdala, the paraventricular, dorsomedial and ventromedial hypothalamus, the periaqueductal grey matter, the dorsal raphe, and the median raphe nucleus. Chronic treatment with corticosterone also increased CRFR1-immunoreactivity in the ventrolateral septum, central amygdala, dorsomedial hypothalamus, ventral region of the dorsal raphe and median raphe. These results contribute to a better understanding of the behavioral and neurobiological alterations induced by chronic exposure to glucocorticoids.

Anxiolytic and panicolytic-like effects of environmental enrichment seem to be modulated by serotonin neurons located in the dorsal subnucleus of the dorsal raphe.

In a previous study, we showed that exposure of rats to a one-week environmental enrichment (EE) protocol decreases elevated T-maze (ETM) avoidance responses, an anxiolytic-like effect, without altering escape reactions, in clinical terms related to panic disorder. These anxiolytic-like effects were followed by decreased delta FosB-immunoreactivity (delta FosB-ir) in the cingulate cortex, dorsolateral and intermediate lateral septum, hippocampus (cornus of Ammon), anterior and dorsomedial hypothalamus, medial and basolateral amygdala and ventral region of the dorsal raphe nucleus. The purpose of the present study was to further investigate behavioral and neurophysiological alterations induced by EE exposure. For that, in a first experiment we verified if increasing the time of exposure to the same EE protocol used in our previous study (from one to two weeks) altered male Wistar rats' ETM escape responses. All animals were tested in an open field, immediately after the ETM, for locomotor activity assessment. Since anxiety and panic-related reactions have been associated to the functioning of specific subnuclei of the dorsal raphe nucleus (DR), we also evaluated delta FosB-ir in serotonergic cells of DR regions. At last, we analyzed plasma corticosterone levels in animals submitted to EE and to standard housing. Results showed that a two-week exposure to EE decreases both ETM avoidance and escape reactions, inducing anxiolytic and panicolytic-like effects, respectively. There was also a significant decrease in the number of double staining neurons in the midrostral region of the dorsal subnucleus of the dorsal raphe. No changes in corticosterone levels, however, were observed. These results contribute to a better understanding of the effects of EE on anxiety and panic-related responses.

Effects of acute restraint and unpredictable chronic mild stress on brain corticotrophin releasing factor mRNA in the elevated T-maze.

Corticotrophin releasing factor (CRF) modulates stress/anxiety-related responses. Previous studies showed that exposure to acute restraint and unpredictable chronic mild stress (UCMS) facilitates elevated T-maze (ETM) avoidance responses, an anxiogenic-like effect. This study verified the role of CRF in the modulation of ETM avoidance and escape reactions, in unstressed rats and in animals exposed to acute restraint or to UCMS, by quantifying CRF mRNA concentrations in stress/anxiety-related brain regions, through semiquantitative in situ hybridization. Results showed that stress exposure altered CRF mRNA in regions related to the modulation of stress/anxiety: the cingulate cortex, the hippocampus, the paraventricular and dorsomedial hypothalamus, the medial and central amygdalas, the dorsal region of the dorsal raphe (dDR) and the ventrolateral periaqueductal gray. A regression analysis showed that the anxiogenic-like effects observed in acute restraint animals were particularly associated to increases in CRF mRNA in the paraventricular hypothalamus, medial and central amygdalas and dDR. On the other hand, anxiogenic-like effects observed after UCMS exposure are associated to increases in CRF mRNA in the medial and central amygdalas, in the BNST and in the ventrolateral periaqueductal grey. This observation suggests important differences in the neurocircuitry that mediates responses to acute and chronic stress exposure. CRF mRNA in regions traditionally related to the modulation of panic reactions (the dorsal periaqueductal grey and the lateral wings of the dorsal raphe) were not observed, what might explain the absence of panicogenic-like effects of stress exposure. These results contribute to a better understanding of the role played by CRF in stress/anxiety-related responses.

Environmental enrichment decreases avoidance responses in the elevated T-maze and delta FosB immunoreactivity in anxiety-related brain regions.

Environmental enrichment (EE) is an animal management technique, which seems to improve adaptation to the experimental conditions of housing in laboratory animals. Previous studies have pointed to different beneficial effects of the procedure in the treatment of several disorders, including psychiatric conditions such as depression. The anxiolytic effects induced by EE, on the other hand, are not as clear. In fact, it has been proposed that EE acts as a mild stressor agent. To better understand the relationship of EE with anxiety-related responses, the present study exposed rats to one week of EE and subsequently tested these animals in the inhibitory avoidance and escape tasks of the elevated T-maze (ETM). In clinical terms, these responses have been respectively related to generalized anxiety and panic disorder. All animals were tested in an open field, immediately after the ETM, for locomotor activity assessment. Additionally, analysis of delta FosB protein immunoreactivity (FosB-ir) was used to map areas activated by EE exposure and plasma corticosterone measurements were performed. The results obtained demonstrate that exposure to EE for one week impaired avoidance responses, an anxiolytic-like effect, without altering escape reactions. Also, in animals submitted to the avoidance task EE exposure decreased FosB-ir in the cingulate cortex, dorsolateral and intermediate lateral septum, hippocampus (cornus of Ammon), anterior and dorsomedial hypothalamus, medial and basolateral amygdala and ventral region of the dorsal raphe nucleus. Although no behavioral differences were observed in animals submitted to the escape task, EE exposure also decreased FosB-ir in the cingulate cortex, hippocampus (dentate gyrus), lateral amygdala, paraventricular, anterior and ventromedial hypothalamus, dorsomedial periaqueductal gray and ventral and dorsal region of the dorsal raphe. No changes in corticosterone levels, however, were observed. These results contribute to a better understanding of the effects of EE on anxiety.