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1.
J Bioenerg Biomembr ; 56(4): 373-387, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38869808

RESUMO

Hypercholesterolemia is one of the most important risk factors for cardiovascular diseases. However, it is mostly associated with vascular dysfunction and atherosclerotic lesions, while evidence of direct effects of hypercholesterolemia on cardiomyocytes and heart function is still incomplete and controversial. In this study, we assessed the direct effects of hypercholesterolemia on heart function and the electro-contractile properties of isolated cardiomyocytes. After 5 weeks, male Swiss mice fed with AIN-93 diet added with 1.25% cholesterol (CHO), developed an increase in total serum cholesterol levels and cardiomyocytes cholesterol content. These changes led to altered electrocardiographic records, with a shortening of the QT interval. Isolated cardiomyocytes displayed a shortening of the action potential duration with increased rate of depolarization, which was explained by increased IK, reduced ICa.L and altered INa voltage-dependent inactivation. Also, reduced diastolic [Ca2+]i was found with preserved adrenergic response and cellular contraction function. However, contraction of isolated hearts is impaired in isolated CHO hearts, before and after ischemia/reperfusion, although CHO heart was less susceptible to arrhythmic contractions. Overall, our results demonstrate that early hypercholesterolemia-driven increase in cellular cholesterol content is associated with direct modulation of the heart and cardiomyocytes' excitability, Ca2+ handling, and contraction.


Assuntos
Hipercolesterolemia , Miócitos Cardíacos , Animais , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Hipercolesterolemia/fisiopatologia , Hipercolesterolemia/metabolismo , Hipercolesterolemia/patologia , Camundongos , Masculino
2.
Behav Pharmacol ; 35(1): 4-13, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38375658

RESUMO

Minocycline is a tetracycline antibiotic with off-label use as an anti-inflammatory drug. Because it can cross the blood-brain barrier, minocycline has been proposed as an alternative treatment for psychiatric disorders, in which inflammation plays an important role. However, its beneficial effects on anxiety disorders are unclear. Therefore, we performed a systematic review and meta-analysis to evaluate the efficacy of minocycline as an anxiolytic drug in preclinical models. We performed a PubMed search according to the PRISMA guidelines and PICOS strategy. The risk of bias was evaluated using the SYRCLE tool. We included studies that determined the efficacy of minocycline in animal models of anxiety that may involve exposures (e.g. stressors, immunomodulators, injury). Data extracted included treatment effect, dose range, route of administration, and potential mechanisms for the anxiolytic effect. Meta-analysis of twenty studies showed that minocycline reduced anxiety-like behavior in rodents previously exposed to stress or immunostimulants but not in exposure-naïve animals. This effect was not associated with the dose administered or treatment duration. The mechanism for the anxiolytic activity of minocycline may depend on its anti-inflammatory effects in the brain regions involving anxiety. These suggest that minocycline could be repurposed as a treatment for anxiety and related disorders and warrants further evaluation.


Assuntos
Ansiolíticos , Minociclina , Humanos , Camundongos , Animais , Minociclina/farmacologia , Ansiolíticos/farmacologia , Modelos Animais de Doenças , Antibacterianos/uso terapêutico , Anti-Inflamatórios
3.
Artif Organs ; 48(6): 626-635, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38149317

RESUMO

BACKGROUND: Electrotactile systems are compact interfaces that can be used to convey information through the skin by producing a range of haptic sensations. In many applications, however, the user needs to perceive and interpret haptic stimulation while being engaged in parallel activities. Developing methods that ensure reliable recognition of electrotactile messages despite additional cognitive load is, therefore, an important step for the practical application of electrotactile displays. METHODS: This study investigated if a simple strategy of repeating electrotactile messages can improve message identification during multitasking. Ten participants identified 36 spatiotemporal electrotactile messages delivered through a 3 × 2 pad-matrix electrode placed on the torso while performing a concomitant cognitive task in three conditions: the messages were presented once (No-REP), and each message was repeated three (REP3) and five (REP5) times. The main outcome measure was the success rate (SR) of message identification. RESULTS: During multitasking, in the No-REP condition, the SR (median (IQR)) dropped to 56.25% (22.62%), demonstrating that the cognitive task decreased performance. However, the SR significantly improved with message repetitions, reaching 72.92% (21.87%) and 81.25% (18.66%) in REP3 and REP5 conditions respectively, without a statistically significant difference between REP3 and REP5. CONCLUSIONS: Multitasking affected the efficacy of haptic communication, but message repetition was shown to be an effective strategy for improving performance. Additionally, only three repetitions were enough, as an additional increase in the duration of message transmission (5 repetitions) did not lead to further improvement. This study is an important step toward delivering electrotactile communication that can cope with the demands of real-world applications.


Assuntos
Cognição , Eletrodos , Tato , Humanos , Masculino , Cognição/fisiologia , Feminino , Tato/fisiologia , Adulto Jovem , Adulto , Desenho de Equipamento
4.
J Appl Biomech ; 40(3): 241-249, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38604601

RESUMO

This study estimated the contribution of the midfoot joint complex (MJC) kinematics to the pelvis anterior-posterior positions during the stance phase of walking and investigated whether the MJC is functionally coordinated with the lower limb joints to maintain similar pelvic positions across steps. Hip, knee, ankle, and MJC sagittal angles were measured in 11 nondisabled participants during walking. The joints' contributions to pelvic positions were computed through equations derived from a link-segment model. Functional coordination across steps was identified when the MJC contribution to pelvic position varied and the summed contributions of other joints varied in the opposite direction (strong negative covariations [r ≤ -.7] in stance phase instants). We observed that the MJC plantarflexion (arch raising) during the midstance and late stance leads the pelvis backward, avoiding excessive forward displacement. The MJC was the second joint that contributed most to the pelvis positions (around 18% of all joints' contributions), after the ankle joint. The MJC and ankle were the joints that were most frequently coordinated with the other joints (≅70% of the stance phase duration). The findings suggest that the MJC is part of the kinematic chain that determines pelvis positions during walking and is functionally coordinated with the lower limb joints.


Assuntos
Caminhada , Humanos , Masculino , Caminhada/fisiologia , Fenômenos Biomecânicos , Feminino , Adulto , Extremidade Inferior/fisiologia , Articulação do Tornozelo/fisiologia , Articulações do Pé/fisiologia , Pé/fisiologia , Pelve/fisiologia , Articulação do Quadril/fisiologia
5.
Alzheimers Dement ; 19(6): 2595-2604, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36465055

RESUMO

INTRODUCTION: Depression is frequent among older adults and is a risk factor for dementia. Identifying molecular links between depression and dementia is necessary to shed light on shared disease mechanisms. Reduced brain-derived neurotrophic factor (BDNF) and neuroinflammation are implicated in the pathophysiology of depression and dementia. The exercise-induced hormone, irisin, increases BDNF and improves cognition in animal models of Alzheimer's disease. Lipoxin A4 is a lipid mediator with anti-inflammatory activity. However, the roles of irisin and lipoxin A4 in depression remain to be determined. METHODS: In the present study, blood and CSF were collected from 61 elderly subjects, including individuals with and without cognitive impairment. Screening for symptoms of depression was performed using the 15-item Geriatric Depression Scale (GDS-15). RESULTS: CSF irisin and lipoxin A4 were positively correlated and reduced, along with a trend of BDNF reduction, in elderly individuals with depression, similar to previous observations in patients with dementia. DISCUSSION: Our findings provide novel insight into shared molecular signatures connecting depression and dementia.


Assuntos
Doença de Alzheimer , Lipoxinas , Animais , Depressão/psicologia , Fator Neurotrófico Derivado do Encéfalo , Fibronectinas , Brasil
6.
Acta Neuropsychiatr ; : 1-8, 2023 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-37968964

RESUMO

OBJECTIVE: Preclinical studies suggest that cannabidiol (CBD), a non-intoxicating phytocannabinoid, may reduce addiction-related behaviours for various drug classes in rodents, including ethanol, opiates, and psychostimulants. CBD modulates contextual memories and responses to reward stimuli. Nonetheless, research on the impact of CBD on cocaine addiction-like behaviors is limited and requires further clarification. This study tested the hypothesis that CBD administration inhibits the acquisition and retrieval of cocaine-induced conditioned place preference (CPP) in adult male and female C57BL6/J mice. We also ought to characterise a 5-day CPP protocol in these animals. METHODS: Male and female C57BL/6J mice were administered CBD (3, 10, and 30 mg/kg) 30 minutes before cocaine (15 mg/kg) acquisition of expression of CPP. RESULTS: Cocaine induces a CPP in both female and male mice in the 5-day CPP protocol. CBD failed to prevent the acquisition or retrieval of place preference induced by cocaine. CBD did not decrease the time spent on the side paired with cocaine at any of the doses tested in male and female mice, in either acquisition or expression of contextual memory. CONCLUSION: This study found no support for the hypothesis that CBD decreases reward memory involved in the formation of cocaine addiction. Further research is necessary to investigate the involvement of CBD in other behavioural responses to cocaine and other psychostimulant drugs. This study, however, characterised a 5-day CPP protocol for both female and male C57BL/6J mice.

7.
Acta Neuropsychiatr ; : 1-10, 2023 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-37982167

RESUMO

OBJECTIVE: The transient receptor potential cation channel, subfamily V (vanilloid), member 1 (TRPV1) mediates pain perception to thermal and chemical stimuli in peripheral neurons. The cannabinoid receptor type 1 (CB1), on the other hand, promotes analgesia in both the periphery and the brain. TRPV1 and CB1 have also been implicated in learned fear, which involves the association of a previously neutral stimulus with an aversive event. In this review, we elaborate on the interplay between CB1 receptors and TRPV1 channels in learned fear processing. METHODS: We conducted a PubMed search for a narrative review on endocannabinoid and endovanilloid mechanisms on fear conditioning. RESULTS: TRPV1 and CB1 receptors are activated by a common endogenous agonist, arachidonoyl ethanolamide (anandamide), Moreover, they are expressed in common neuroanatomical structures and recruit converging cellular pathways, acting in concert to modulate fear learning. However, evidence suggests that TRPV1 exerts a facilitatory role, whereas CB1 restrains fear responses. CONCLUSION: TRPV1 and CB1 seem to mediate protective and aversive roles of anandamide, respectively. However, more research is needed to achieve a better understanding of how these receptors interact to modulate fear learning.

8.
Immunology ; 165(3): 355-368, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34964126

RESUMO

Mucositis is a major clinical complication associated with cancer treatment and may limit the benefit of chemotherapy. Leukocytes and inflammatory mediators have been extensively associated with mucositis severity. However, the role of eosinophils in the pathophysiology of chemotherapy-induced mucositis remains to be elucidated. Here, using GATA-1-deficient mice, we investigated the role of eosinophils in intestinal mucositis. There was marked accumulation of eosinophils in mice given irinotecan and eosinophil ablation inhibited intestinal mucositis. Treatment with Evasin-4, a chemokine receptor antagonist, reduced the recruitment of eosinophils and decreased irinotecan-induced mucositis. Importantly, Evasin-4 did not interfere negatively with the antitumour effects of irinotecan. Evasin-4 was of benefit for mice given high doses of irinotecan once Evasin-4-treated mice presented delayed mortality. Altogether, our findings suggest that Evasin-4 may have significant mucosal-protective effects in the context of antineoplastic chemotherapy and may, therefore, be useful in combination with anticancer treatment in cancer patients.


Assuntos
Antineoplásicos , Mucosite , Animais , Antineoplásicos/uso terapêutico , Camptotecina/efeitos adversos , Eosinófilos/patologia , Humanos , Mucosa Intestinal/patologia , Irinotecano/efeitos adversos , Camundongos , Mucosite/induzido quimicamente , Mucosite/tratamento farmacológico , Mucosite/patologia
9.
Behav Pharmacol ; 33(2&3): 90-104, 2022 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-33491992

RESUMO

Drug abuse and addiction can be initiated and reinstated by contextual stimuli previously paired with the drug use. The influence exerted by the context on drug-seeking behaviour can be modelled in experimental animals with place-conditioning protocols. Here, we review the effects of cannabinoids in place conditioning and the therapeutic potential of the endocannabinoid system for interfering with drug-related memories. The phytocannabinoid Δ9-tetrahydrocannabinol (THC) tends to induce conditioned place preference (CPP) at low doses and conditioned place aversion at high doses; cannabidiol is devoid of any effect, yet it inhibits CPP induced by some drugs. Synthetic CB1 receptor agonists tend to recapitulate the biphasic profile observed with THC, whereas selective antagonists/inverse agonists inhibit CPP induced by cocaine, nicotine, alcohol and opioids. However, their therapeutic use is limited by potential psychiatric side effects. The CB2 receptor has also attracted attention, because selective CB2 receptor agonists inhibit cocaine-induced CPP. Inhibitors of endocannabinoid membrane transport and hydrolysis yield mixed results. In targeting the endocannabinoid system for developing new treatments for drug addiction, future research should focus on 'neutral' CB1 receptor antagonists and CB2 receptor agonists. Such compounds may offer a well-tolerated pharmacological profile and curb addiction by preventing drug-seeking triggered by conditioned contextual cues.


Assuntos
Cocaína , Endocanabinoides , Animais , Cocaína/farmacologia , Dronabinol/farmacologia , Receptor CB1 de Canabinoide , Receptor CB2 de Canabinoide
10.
Behav Pharmacol ; 33(2&3): 213-221, 2022 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-34074811

RESUMO

The endocannabinoid system modulates the stress coping strategies in the dorsolateral periaqueductal grey (dlPAG). The most relevant endocannabinoids, anandamide and 2-arachidonoylglycerol (2-AG) exert inhibitory control over defensive reactions mediated by the dlPAG. However, the protective role of anandamide is limited by its lack of effect in higher concentrations. Thus, the 2-AG emerges as a complementary target for developing new anxiolytic compounds. Nevertheless, the role of 2-AG on stress responsivity may vary according to the nature of the stimulus. In this study, we verified whether the dlPAG injection of 2-AG or inhibitors of its hydrolysis induce anxiolytic-like effects in male Wistar rats exposed to behavioral models in which physical stress (mild electric shock) is a critical component, namely the contextual fear conditioning test (CFC) and the Vogel conflict test (VCT). We also investigated the contribution of cannabinoid receptor type 1 (CB1) and type 2 (CB2) in such effects. The facilitation of 2-AG signaling in the dlPAG reduced contextual fear expression and exhibited an anxiolytic-like effect in the VCT in a mechanism dependent on activation of CB1 and CB2. However, the VCT required a higher dose than CFC. Further, the monoacylglycerol inhibitors, which inhibit the hydrolysis of 2-AG, were effective only in the CFC. In conclusion, we confirmed the anti-aversive properties of 2-AG in the dlPAG through CB1 and CB2 mechanisms. However, these effects could vary according to the type of stressor and the anxiety model employed.


Assuntos
Ansiolíticos , Endocanabinoides , Animais , Ansiolíticos/metabolismo , Ansiolíticos/farmacologia , Ácidos Araquidônicos , Endocanabinoides/metabolismo , Endocanabinoides/farmacologia , Medo , Glicerídeos , Masculino , Substância Cinzenta Periaquedutal/metabolismo , Piperidinas/farmacologia , Pirazóis/farmacologia , Ratos , Ratos Wistar , Receptor CB1 de Canabinoide/metabolismo
11.
Behav Pharmacol ; 33(1): 2-14, 2022 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-33136616

RESUMO

The transient receptor potential vanilloid-1 channel (TRPV1) is responsible for decoding physical and chemical stimuli. TRPV1 is activated by capsaicin (a compound from chili peppers), heat (above 43°C) and acid environment, playing a major role in pain, inflammation and body temperature. Molecular and histological studies have suggested TRPV1 expression in specific brain regions, where it can be activated primarily by the endocannabinoid anandamide, fostering studies on its potential role in psychiatric disorders. TRPV1 blockers are effective in various animal models predictive of anxiolytic and antipanic activities, in addition to reducing conditioned fear. In models of antidepressant activity, these compounds reduce behavioral despair and promote active stress-coping behavior. TRPV1 blockers also reduce the effects of certain drugs of abuse and revert behavioral changes in animal models of neurodevelopmental disorders. The main limiting factor in developing TRPV1 blockers as therapeutic agents concerns their effects on body temperature, particularly hyperthermia. New compounds, which block specific states of the channel, could represent an alternative. Moreover, compounds blocking both TRPV1 and the anandamide-hydrolyzing enzyme, fatty acid amide hydrolase (FAAH), termed dual TRPV1/FAAH blockers, have been investigated with promising results. Overall, preclinical studies yield favorable results with TRPV1 blockers in animal models of psychiatric disorders.


Assuntos
Amidoidrolases/antagonistas & inibidores , Encéfalo , Transtornos Mentais , Canais de Cátion TRPV/antagonistas & inibidores , Amidoidrolases/metabolismo , Analgésicos/farmacologia , Animais , Ansiolíticos/farmacologia , Antidepressivos/farmacologia , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Desenvolvimento de Medicamentos , Humanos , Transtornos Mentais/tratamento farmacológico , Transtornos Mentais/metabolismo , Transtornos Mentais/psicologia , Canais de Cátion TRPV/metabolismo
12.
Artif Organs ; 46(10): 2044-2054, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35712803

RESUMO

BACKGROUND: Tactile stimulation can be used to convey information to a user in different scenarios while avoiding overloading other senses. Tactile messages can be transmitted as spatial patterns, potentially allowing for a high information throughput. The aim of the present study was to design and test different encoding schemes to determine the best approach for conveying spatial patterns. METHODS: Encoding schemes with simultaneous (SIM) and sequential pad activation (SEQ) were evaluated, including four SEQ variants designed to potentially facilitate the recognition. In SEQ-col and SEQ-row, the column and row of the activated pad were signified using different frequencies, while SEQ-all and SEQ-all-fast included the activation of all pads where those belonging to the pattern were indicated by changes in frequency (ON pads). The success rate (SR) of the pattern identification and the response time were quantified in 15 participants who recognized 20 patterns delivered through a 3 × 2 pad matrix placed on the lateral torso. RESULTS: SIM was not a feasible method to present the patterns (median, 15%; IQR, 5%). The SR improved with SEQ (median, 60%; IQR, 20%) and further increased with additional cues, particularly with SEQ-row (median, 78.3%; IQR, 23.3%) and SEQ-all (median, 96.7%; IQR, 5%). Importantly, the stimulation time of SEQ-all could be decreased without a substantial drop in accuracy (SEQ-all-fast: median, 89.2%; IQR, 19.2%). CONCLUSIONS: The spatiotemporal stimulation with sequential activation of all pads (SEQ-all) seems to be the method of choice when conveying tactile messages as spatial patterns. This is an important outcome for increasing the information bandwidth of communication through the tactile channel.


Assuntos
Percepção do Tato , Tato , Estimulação Elétrica , Eletrodos , Humanos , Pele , Tronco , Tato/fisiologia , Percepção do Tato/fisiologia
13.
Metab Brain Dis ; 37(8): 2711-2718, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36040711

RESUMO

The excessive consumption of ultra-processed foods and the development of obesity has been associated with several comorbidities, including psychiatric disorders. Excess fat tissue promotes a low-intensity inflammatory state, mainly in the white tissue, which is essential in developing metabolic alterations and influences brain homeostasis. In this scenario, Cannabidiol (CBD), a compound from Cannabis sativa, has presented anxiolytic and anti-inflammatory effects in murine models. This study verified whether CBD treatment would ameliorate the compulsive-like and anxiety-like behaviors observed after mice's chronic consumption of a high-refined carbohydrate (HC) diet. BALB/c male mice received a control or HC diet for 12 weeks followed by vehicle and CBD (30 mg/Kg, i.p.) administration, and their behavior was evaluated in the Marble Burying test (MB) and Novel Suppressing Feeding test (NSF). The sub-chronic, but not acute, treatment with CBD attenuated the compulsive-like and anxiogenic-like behavior induced by the HC diet. Our data reinforced the harmful effects of the HC diet's chronic consumption on compulsive and anxious behaviors and the potential of CBD as a drug treatment for psychiatric disorders associated with obesity.


Assuntos
Canabidiol , Camundongos , Masculino , Animais , Canabidiol/farmacologia , Canabidiol/uso terapêutico , Camundongos Endogâmicos BALB C , Comportamento Compulsivo/induzido quimicamente , Comportamento Compulsivo/tratamento farmacológico , Obesidade/induzido quimicamente , Obesidade/tratamento farmacológico , Carboidratos
14.
Sensors (Basel) ; 22(21)2022 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-36366029

RESUMO

This paper shows the performance resulting from combining vector sensor directional components in an underwater acoustic communication experiment. The objective is to relate performance with transmission direction and range. Receiver structures based on beamforming and passive time-reversal are tested in order to quantify and compare the steerability impact of vector sensor directional components. A shallow water experiment is carried out with a bottom fixed two-axis pressure-gradient vector sensor. A ship suspended acoustic source transmits coherent modulated communication signals at various ranges and from several directions. Results show that one vector sensor can provide an up to 10 times smaller error bit rate than a pressure sensor, favoring communication robustness without size penalty.

15.
Sensors (Basel) ; 22(19)2022 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-36236758

RESUMO

Electrotactile stimulation is a technology that reproducibly elicits tactile sensations and can be used as an alternative channel to communicate information to the user. The presented work is a part of an effort to develop this technology into an unobtrusive communication tool for first responders. In this study, the aim was to compare the success rate (SR) between discriminating stimulation at six spatial locations (static encoding) and recognizing six spatio-temporal patterns where pads are activated sequentially in a predetermined order (dynamic encoding). Additionally, a procedure for a fast amplitude calibration, that includes a semi-automated initialization and an optional manual adjustment, was employed and evaluated. Twenty subjects, including twelve first responders, participated in the study. The electrode comprising the 3 × 2 matrix of pads was placed on the lateral torso. The results showed that high SRs could be achieved for both types of message encoding after a short learning phase; however, the dynamic approach led to a statistically significant improvement in messages recognition (SR of 93.3%), compared to static stimulation (SR of 83.3%). The proposed calibration procedure was also effective since in 83.8% of the cases the subjects did not need to adjust the stimulation amplitude manually.


Assuntos
Tronco , Tato , Calibragem , Comunicação , Estimulação Elétrica/métodos , Eletrodos , Humanos , Tato/fisiologia
16.
Neurobiol Learn Mem ; 180: 107422, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33691195

RESUMO

N-methyl D-aspartate (NMDA) administered at subtoxic dose plays a protective role against neuronal excitotoxicity, a mechanism described as preconditioning. Since the activation of adenosinergic receptors influences the achievement of NMDA preconditioning in the hippocampus, we evaluated the potential functional interplay between adenosine A1 and A2A receptors (A1R and A2AR) activities and NMDA preconditioning. Adult male Swiss mice received saline (NaCl 0.9 g%, i.p.) or a nonconvulsant dose of NMDA (75 mg/kg, i.p.) and 24 h later they were treated with the one of the ligands: A1R agonist (CCPA, 0.2 mg/kg, i.p.) or antagonist (DPCPX, 3 mg/kg, i.p.), A2AR agonist (CGS21680, 0.05 mg/kg, i.p.) or antagonist (ZM241385, 0.1 mg/kg, i.p.) and subjected to contextual fear conditioning task. Binding properties and content of A2AR and glutamate uptake were assessed in the hippocampus of mice subjected to NMDA preconditioning. Treatment with CGS21680 increased the time of freezing during the exposure of animals to the new environment. NMDA preconditioning did not affect the freezing time of mice per se, but it prevented the response observed after the activation of A2AR. Furthermore, the activation of A2AR by CGS21680 after the preconditioning blocked the increase of glutamate uptake induced by NMDA preconditioning. The immunodetection of A2AR in total hippocampal homogenates showed no significant differences evoked by NMDA preconditioning and did not alter A2AR maximum binding for the selective ligand [3H]CGS21680. These results demonstrate changes in A2AR functionality in mice following NMDA preconditioning.


Assuntos
Condicionamento Clássico/fisiologia , Medo , Ácido Glutâmico/metabolismo , Hipocampo/metabolismo , Memória/fisiologia , Receptor A1 de Adenosina/metabolismo , Receptor A2A de Adenosina/metabolismo , Agonistas do Receptor A1 de Adenosina/farmacologia , Antagonistas do Receptor A1 de Adenosina/farmacologia , Agonistas do Receptor A2 de Adenosina/farmacologia , Antagonistas do Receptor A2 de Adenosina/farmacologia , Animais , Condicionamento Clássico/efeitos dos fármacos , Agonistas de Aminoácidos Excitatórios/farmacologia , Hipocampo/efeitos dos fármacos , Memória/efeitos dos fármacos , Camundongos , N-Metilaspartato/farmacologia
17.
Behav Pharmacol ; 32(2&3): 182-193, 2021 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-33136614

RESUMO

Panic disorder can be categorized into the nonrespiratory or the respiratory subtypes, the latter comprising dyspnea, shortness of breath, chest pain, feelings of suffocation, and paresthesias. Doxapram is an analeptic capable of inducing panic attacks with respiratory symptoms in individuals diagnosed with the disorder; however, its neuroanatomical targets and its effects on experimental animals remain uncharacterized. One of the brain regions proposed to trigger panic attacks is the midbrain periaqueductal gray (PAG). Therefore, in this study, we evaluated the effects of doxapram in Fos (c-Fos) protein expression in the PAG and characterized its cardiorespiratory and behavioral effects on the elevated T maze and in the conditioned place aversion (CPA) paradigms. Doxapram increased Fos expression in different columns of the PAG, increased respiratory frequency, decreased heart rate, and increased arterial pressure when injected via intravenous route. Alprazolam, a panicolytic benzodiazepine, injected via intraperitoneal route, decreased respiratory frequency, whereas URB597, an anandamide hydrolysis inhibitor injected via intraperitoneal route, was ineffective. Doxapram injected via intraperitoneal route induced an anxiogenic-like effect in the elevated T-maze model; however, it failed to induce CPA. This study suggests that the cardiorespiratory and behavioral effects of doxapram in rodents serve as an experimental model that can provide insights into the neurobiology of panic attacks.


Assuntos
Estimulantes do Sistema Nervoso Central/farmacologia , Doxapram/farmacologia , Transtorno de Pânico/fisiopatologia , Administração Intravenosa , Alprazolam/farmacologia , Animais , Benzamidas/farmacologia , Carbamatos/farmacologia , Estimulantes do Sistema Nervoso Central/administração & dosagem , Modelos Animais de Doenças , Doxapram/administração & dosagem , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Substância Cinzenta Periaquedutal/efeitos dos fármacos , Substância Cinzenta Periaquedutal/metabolismo , Proteínas Proto-Oncogênicas c-fos/metabolismo , Ratos , Ratos Wistar
18.
Behav Pharmacol ; 32(1): 2-8, 2021 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-33399294

RESUMO

The pyridobenzoxazepine compound, 5-(4-methylpiperazin-1-yl)-8-chloro-pyrido[2,3-b][1,5]benzoxazepine (JL13), has been developed as a potential antipsychotic drug. We tested the hypothesis that JL13 is efficacious in both dopaminergic and glutamatergic animal models of schizophrenia. We investigated JL13 for its efficacy to prevent cocaine- and ketamine-induced hyperlocomotion and MK-801-induced deficits in prepulse inhibition (PPI) of the startle reflex. Male Swiss mice received injections of JL13 (0.1-10 mg/kg) and were tested in the open field for basal locomotion. In separate experiments, the animals received injections of JL13 (0.1-3 mg/kg) followed by cocaine (10 mg/kg), ketamine (60 mg/kg), or MK-801 (0.5 mg/kg) and were tested in the open field for hyperlocomotion. In addition, it was also tested if JL13 prevented MK-801-induced disruption of PPI. Only the highest dose of JL13 impaired spontaneous locomotion, suggesting its favorable profile regarding motor side effects. At doses that did not impair basal motor activity, JL13 prevented cocaine-, ketamine-, and MK-801-induced hyperlocomotion. Moreover, JL13 prevented MK-801-induced disruption of PPI. Extending previous findings, this study shows that JL13 exerts antipsychotic-like activity in both dopaminergic and glutamatergic models. This compound has a favorable pharmacological profile, similar to second-generation antipsychotics.


Assuntos
Antipsicóticos/farmacologia , Oxazepinas/farmacologia , Piperazinas/farmacologia , Piridinas/farmacologia , Esquizofrenia/tratamento farmacológico , Animais , Antipsicóticos/administração & dosagem , Cocaína/farmacologia , Modelos Animais de Doenças , Maleato de Dizocilpina/farmacologia , Dopamina/metabolismo , Relação Dose-Resposta a Droga , Ácido Glutâmico/metabolismo , Ketamina/farmacologia , Locomoção/efeitos dos fármacos , Masculino , Camundongos , Oxazepinas/administração & dosagem , Piperazinas/administração & dosagem , Piridinas/administração & dosagem , Reflexo de Sobressalto/efeitos dos fármacos , Esquizofrenia/fisiopatologia
19.
Epilepsy Behav ; 121(Pt B): 106832, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-31839498

RESUMO

This review focuses on the possible roles of phytocannabinoids, synthetic cannabinoids, endocannabinoids, and "transient receptor potential cation channel, subfamily V, member 1" (TRPV1) channel blockers in epilepsy treatment. The phytocannabinoids are compounds produced by the herb Cannabis sativa, from which Δ9-tetrahydrocannabinol (Δ9-THC) is the main active compound. The therapeutic applications of Δ9-THC are limited, whereas cannabidiol (CBD), another phytocannabinoid, induces antiepileptic effects in experimental animals and in patients with refractory epilepsies. Synthetic CB1 agonists induce mixed effects, which hamper their therapeutic applications. A more promising strategy focuses on compounds that increase the brain levels of anandamide, an endocannabinoid produced on-demand to counteract hyperexcitability. Thus, anandamide hydrolysis inhibitors might represent a future class of antiepileptic drugs. Finally, compounds that block the TRPV1 ("vanilloid") channel, a possible anandamide target in the brain, have also been investigated. In conclusion, the therapeutic use of phytocannabinoids (CBD) is already in practice, although its mechanisms of action remain unclear. Endocannabinoid and TRPV1 mechanisms warrant further basic studies to support their potential clinical applications. This article is part of the Special Issue "NEWroscience 2018".


Assuntos
Canabidiol , Canabinoides , Cannabis , Epilepsia , Animais , Canabidiol/uso terapêutico , Canabinoides/uso terapêutico , Dronabinol , Epilepsia/tratamento farmacológico , Humanos
20.
An Acad Bras Cienc ; 93(suppl 3): e20201486, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34644723

RESUMO

Pinus greggii has potential for inclusion in temperate zone breeding programs around the world as it is frost resistant and produces high yields for pulp production. This study estimates the genetic parameters for two P. greggii progeny tests established in Telêmaco Borba, Paraná, Brazil. We evaluated diameter at breast height (DBH) and total height (H) at seven and nine years of age. The narrow-sense heritability ( h i 2 ) ranged from 0.225 (H, 7 years) to 0.515 (H, 9 years). The genetic correlation was high for all traits, reaching up to 0.91 between traits and 0.94 between ages. In addition, the results show the presence of Genotype x Environment interaction, and as such, the most productive and stable progeny were identified based on the Harmonic Mean of the Relative Performance of Genetic Values (MHPRVG) values. These population has genetic materials that are superior in terms of both DBH and H compared to the control and to P. greggii materials analyzed internationally. Our results contribute to the literature by providing further genetic information on this species, while also demonstrating the implications of thinning for genetic gains and effective population size.


Assuntos
Pinus , Brasil , Interação Gene-Ambiente , Genótipo , Fenótipo , Pinus/genética , Melhoramento Vegetal
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