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1.
Artigo em Inglês | MEDLINE | ID: mdl-38771090

RESUMO

Cavernous malformations (CMs) are rare, often oligosymptomatic vascular lesions. Common manifestations include seizures and focal neurological deficits. Depending on the symptoms, location, size, and risk factors of bleeding, such as the presence of a developmental venous anomaly, the injury can be highly morbid. Hence, one can consider surgical resection. Deep and eloquently located CMs, such as those located in the temporal trunk, can be quite challenging and require an exact operative technique.1-7 We present a 27-year-old patient with a history of headaches that began two years ago and significantly worsened in the last month, associated with visual blurring, scotomas, nausea, phonophobia, and photophobia as well as paresthesias in the hands and perioral region. Imaging investigation revealed a CM in the temporal stem (Zabramski classification II). Owing to the risk of rebleeding and the young age, surgical resection was performed using a transsylvian approach to preserve the temporal cortex. We describe the technique applied and demonstrate the necessary care manipulating the distal sylvian fissure and the superficial sylvian veins. We also detail the anatomy of the temporal stem and the benefit of the transsylvian approach to preserve the white matter fibers that compose the temporal stem. The patient consented to the procedure and to the publication of his/her image. This study was approved by the Ethics Committee of our institution. Performed CM resection using the transsylvian pterional craniotomy technique, and it proceeded without complications. The postoperative period was also uneventful. The postoperative imaging demonstrated total resection of the cavernoma.

2.
Front Neurol ; 15: 1355338, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38751883

RESUMO

Introduction: Deep cavernomas of eloquent areas, located in the region of the basal nuclei and thalamus, account for 9 to 36% of these encephalic vascular malformations. Internal capsule cavernomas are particularly challenging, as they are surrounded by important projection fibers and their manipulation can lead to permanent deficits. To demonstrate through surgical cases that cavernomas of the internal capsule can be approached by frontal craniotomy, via the superior frontal sulcus, in a curative manner and with low morbidity. Methods: We presented two cases of cavernomas of the internal capsule operated, whose treatment was microsurgical resection via frontal craniotomy and access to the lesion via the superior frontal sulcus, described step-by-step. To elucidate the rationale behind the decision, we used preoperative images with an emphasis on the patients' tractography and the importance of comparing these images with anatomical specimens dissected in the neuroanatomy and microsurgery laboratory. Results: The two cases of internal capsule cavernomas, one in the anterior limb and the other in the posterior limb, were treated surgically via the superior frontal sulcus. Discussion: Both patients showed radiological cure and clinical improvement in the post-operative segment. The patient consented to the procedure and to the publication of his/her image. Treatment of internal capsule cavernomas via the superior frontal sulcus has proven to be a safe and effective option.

3.
Front Neurol ; 15: 1347289, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38651102

RESUMO

Introduction: Mutations of the phosphatase and tensin homolog (PTEN) gene have been associated with a spectrum of disorders called PTEN hamartoma tumor syndrome, which predisposes the individual to develop various types of tumors and vascular anomalies. Its phenotypic spectrum includes Cowden syndrome (CS), Bannayan-Riley-Ruvalcaba syndrome (BRRS), Proteus syndrome, autism spectrum disorders (ASD), some sporadic cancers, Lhermitte-Duclos disease (LDD), and various types of associated vascular anomalies. Clinical presentation: A previously healthy 27-year-old woman was experiencing visual scintillating scotomas and mild chronic headaches for the past 2 years. The initial computed tomographic (CT) and magnetic resonance imaging (MRI) scans did not reveal any abnormalities, but the possibility of pseudotumor cerebri was considered. Furthermore, a cerebral angiogram showed a posterior fossa dural arteriovenous fistula (dAVF), which was initially treated through embolization. However, in spite of proper treatment, this patient experienced multiple recurrent dAVFs in different locations, requiring multiple embolizations and surgeries. Despite exhibiting altered cerebral perfusion and hemodynamics, the patient did not display any significant symptoms until she experienced a sudden stroke resulting from deep venous thrombosis, which was not associated with any medical procedures or medication use. A comprehensive analysis was performed due to the aggressive nature of the dAVFs. Surprisingly, exome sequencing of a blood sample revealed a PTEN gene variant in chromosome 10, indicative of Cowden syndrome. However, no tumors or other vascular lesions were detected in other systems that would constitute Cowden syndrome. Conclusion: The rapid formation of multiple and complex dAVFs, coupled with not meeting the criteria for any other PTEN-related syndrome, unequivocally leads to the presentation of a novel phenotype of the PTEN germline variant.

4.
World Neurosurg ; 187: 29-34, 2024 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-38593912

RESUMO

BACKGROUND AND OBJECTIVE: Neurosurgery relies heavily on advanced manual skills, necessitating effective training models for skill development. While various models have been utilized, the human placenta has emerged as a promising candidate for microneurosurgical training due to its anatomical similarities with cerebral vasculature. However, existing placenta models have primarily focused on simulating superficial procedures, often neglecting the complexities encountered in deep operative fields during cranial surgeries. METHODS: This study obtained ethical approval and implemented a modified placenta model to address the limitations of existing training models. The key modification involved folding the placenta and placing it within a rigid container, closely mimicking the structural challenges of cranial procedures. The placenta preparation followed a standardized protocol, including the use of specialized equipment for documentation. RESULTS: The primary feature of the modified model is the folded placenta within the rigid container, which replicates cranial anatomy. This innovative approach enables trainees to engage in a comprehensive range of microsurgical exercises, encompassing vessel dissection, aneurysm clipping, tumor resection, and more. The model successfully mirrors the complexities of real cranial procedures, providing a realistic training experience. CONCLUSIONS: The presented modified placenta model serves as an effective tool for simulating the conditions encountered in deep cranial surgeries. By accurately replicating the challenges of deep operative fields, the model significantly enhances the training of neurosurgical residents. It successfully prepares trainees to navigate the intricacies and difficulties inherent in real cranial surgeries, thus contributing to improved surgical skills and readiness for neurosurgical practice.

5.
Artigo em Inglês | MEDLINE | ID: mdl-38683954

RESUMO

Aneurysms of the bifurcation of the internal carotid artery (ICA) represent approximately 5% of intracranial aneurysms and tend to occur in younger patients.1-3 They typically have a superior orientation, in close relationship with the medial (branches of the anterior cerebral artery, segment A1) and lateral (branches of the middle cerebral artery, segment M1) lenticulostriate arteries (LSA), including recurrent artery of Heubner (RAH). RAH commonly originates in the junction of A1 and A2, courses medially to laterally between LSA and anterior cerebral artery, ICA bifurcation, and middle cerebral artery before entering the lateral portion of the anterior perforated substance.4-7 Damage to these arteries are catastrophic. This complex vascular anatomy makes treatment challenging, either endovascular or microsurgical.8-13 We present a video case of microsurgical clipping for the left ICA bifurcation aneurysm. This study was approved by the ethics committee of our institution. The patient, a 46-year-old man, was diagnosed with an unruptured ICA bifurcation aneurysm during workup for intermittent headache. Morphological characteristics of the aneurysm supported intervention over conservative treatment. Digital subtraction angiography showed a prominent proximal RAH crossing between the aneurysm neck and LSA, providing anatomical protection for clip application. Microsurgical clipping was chosen, and the procedure went uneventfully. The patient consented to the procedure and to the publication of his/her image. We discussed and demonstrated throughout the video how we used this anatomic variation and trajectory of the RAH to prevent clipping of LSA unwittingly and achieve complete occlusion of the aneurysm neck.

6.
World Neurosurg ; 182: e471-e477, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38036172

RESUMO

BACKGROUND: Neurosurgical training continuously seeks innovative methods to enhance the acquisition of essential technical skills for neurosurgeons worldwide. While various training models have been employed, few truly replicate real-life conditions optimally. Human placenta is a good model for neurosurgical microsurgery training due to its anatomic similarities to neurovascular structures. Placental vessels exhibit a branching pattern and caliber comparable with intracranial vessels, making them suitable for practicing microsurgical techniques. The study aims to delineate the anatomic zones of the placenta and propose a segmented training model, resulting in a reproducible, cost-effective, and realistic neurosurgical microsurgery training environment. METHODS: Twenty human placentas were meticulously prepared, injected with dyes, and categorized into zones on the basis of anatomic features. Measurements of placental vessels were recorded and compared with cerebral vessels. The placenta was divided into 4 quadrants to facilitate specific training techniques. RESULTS: Our results revealed varying vessel diameters across placental zones, closely resembling cerebral vessels. Different microsurgical techniques were applied to specific placental zones, thereby optimizing training scenarios. The applicability section described exercises such as membrane dissection, vessel skeletonization, aneurysm creation, vascular bypass, and tumor dissection within the placental model, providing detailed guidance on the zones suitable for each exercise. CONCLUSIONS: Human placenta serves as an effective microsurgical training model for neurosurgery, enhancing neurosurgeons' skills through anatomic segmentation. Integrating this model into training programs can significantly contribute to skill acquisition and improved surgical outcomes. Further research is warranted to refine and expand its utilization, complemented by clinical experiences and other simulation tools.


Assuntos
Neurocirurgia , Placenta , Humanos , Gravidez , Feminino , Placenta/irrigação sanguínea , Modelos Anatômicos , Microcirurgia/métodos , Neurocirurgia/educação , Procedimentos Neurocirúrgicos/métodos , Competência Clínica
9.
World Neurosurg ; 175: e481-e491, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37044208

RESUMO

BACKGROUND: Anterior clinoidectomy is an important procedure used in the treatment of a range of diseases of the frontotemporal region, both vascular and tumoral. Mastering this technique requires a high level of manual skills training. The objective of the study was to describe an easily accessible and economical alternative model of anterior clinoidectomy, with a principal focus on the significance of mastering technical skills and training tactile feedback. METHODS: Five cadaveric sheep heads (10 sides) fixed in formalin and alcohol were injected with silicone and used to simulate extradural (5 sides) and intradural (5 sides) routes and 1 head was used to prepare an anatomic specimen for better demonstration of the anatomy of the paraclinoid region. RESULTS: A comparative anatomic analysis between the ovine and human anterior clinoid process was performed. Using cadaveric sheep models, all principal steps of the procedure for both the extradural and the intradural routes were imitated. CONCLUSIONS: A cadaveric sheep head model serves as a good model of anterior clinoidectomy regarding manual skills training and can serve as a good alternative to human cadaveric training.


Assuntos
Craniotomia , Procedimentos Neurocirúrgicos , Humanos , Animais , Ovinos , Procedimentos Neurocirúrgicos/métodos , Craniotomia/métodos , Osso Esfenoide/cirurgia , Base do Crânio/cirurgia , Cadáver
10.
Biomedicines ; 11(2)2023 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-36830920

RESUMO

The present study aimed to characterize the phenomenon of behavioral sensitization to cocaine and to identify neuroanatomical structures involved in the induction and expression phases of this phenomenon. For this, in experiment 1 (induction phase), mice were treated with saline or cocaine every second day for 15 days (conditioning period), in the open-field or in their home-cages. In experiment 2 (expression phase), the same protocol was followed, except that after the conditioning period the animals were not manipulated for 10 days, and after this interval, animals were challenged with cocaine. Neuroanatomical structures involved in the induction and expression phases were identified by stereological quantification of c-Fos staining in the dorsomedial prefrontal cortex (dmPFC), nucleus accumbens core (NAc core and shell (NAc shell), basolateral amygdala (BLA), and ventral tegmental area (VTA). Neuroanatomical analysis indicated that in the induction phase, cocaine-conditioned animals had higher expression of c-Fos in the dmPFC, NAc core, BLA, and VTA, whereas in the expression phase, almost all areas had higher expression except for the VTA. Therefore, environmental context plays a major role in the induction and expression of behavioral sensitization, although not all structures that compose the mesolimbic system contribute to this phenomenon.

11.
Front Pharmacol ; 14: 1100527, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36814501

RESUMO

Introduction: The endocannabinoid system has been implicated in the neurobiology of opioid use disorder. While the CB1 receptor antagonist rimonabant has been shown to block some of the behavioral effects of opioids, studies suggest that the treatment environment (i.e., receiving treatment in the drug-associated environment, and/or novelty) can influence its effects. In the present study, we investigated the role of the treatment environment in the effects of rimonabant on the expression of morphine-induced behavioral sensitization. Methods: Adult female Swiss mice were submitted to a behavioral sensitization protocol, during which they received morphine (20 mg/kg, i.p.) in the open-field apparatus, and were subsequently treated with vehicle or rimonabant (1 or 10 mg/kg, i.p.) either in the open-field, in the home-cage or in an activity box (novel environment). The expression of conditioned locomotion (increased locomotor activity in the open-field apparatus in the absence of morphine) and of morphine-induced behavioral sensitization (increased locomotor activity in animals sensitized to morphine) was evaluated during asubsequent saline and morphine challenge, respectively. Results: Animals treated with morphine expressed behavioral sensitization, showing a significant increase in locomotor activity over time. Animals sensitized to morphine and treated with vehicle in the home-cage expressed conditioned locomotion, an effect that was blocked by home-cage treatment with rimonabant. During a saline challenge, only animals sensitized to morphine and treated with saline in the home-cage expressed morphine-induced conditioned locomotion. All morphine-treated animals that received saline during the treatment phase (control groups) expressed behavioral sensitization during the morphine challenge. Treatment with rimonabant in the open-field and in the activity box, but not in the home-cage, blocked the expression of morphine-induced behavioral sensitization. Discussion: Our findings suggest that CB1 receptor antagonism can modulate conditioned responses to morphine even when administered in the home-cage. However, exposure to the drug-associated environment or to a novel environment is necessary for the expression of rimonabant's effects on morphine-induced behavioral sensitization during a morphine challenge.

13.
Behav Neurosci ; 137(2): 143-153, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36548050

RESUMO

Optimal levels of anxiety are critical to memory consolidation, but maladaptive anxiety can disrupt memory acquisition. Serotonergic activity within the amygdala influences both anxiety-like behavior and aversive memory consolidation. To evaluate the effects of serotoninergic manipulations within the basolateral amygdala (BLA) on anxiety-like behavior and aversive memory in rats tested in the plus-maze discriminative avoidance task (PMDAT). The PMDAT investigates aversive memory and anxiety-like behavior simultaneously in rodents. Three-month-old male Wistar rats received bilateral infusions (1 µL per side) of saline, 8-OH-DPAT (5-HT1 agonist; 10 nmol), WAY100135 (5-HT1 antagonist; 0.9 nmol), ketanserine (5-HT 2 antagonist; 10 nmol), or fluoxetine (serotonin reuptake inhibitor; 1.6 nmol) into the BLA and were submitted to PMDAT training session 15 min later. In the test, 24 hr later, animals were re-exposed to the apparatus without the infusion of drugs, and aversive memory was evaluated. (a) 8-OH-DPAT did not affect memory or anxiety, but impaired avoidance behavior toward the aversive arm during training; (b) fluoxetine, WAY100135 and ketanserin impaired memory formation; (c) ketanserin decreased anxiety-like behavior; and (d) none of the treatments induced motor changes. The results showed that an increase in serotonin (5-HT) availability or the blockade of 5HT1A and 5HT2A BLA receptors impaired aversive memory formation. However, only 5HT2A receptor antagonism induced anxiolytic effects. Thus, both memory and anxiety-like behavior can be modified by changes in serotonergic transmission in the basolateral amygdala, but the effects on both phenomena seem to be mediated by different mechanisms related to serotonergic transmission. (PsycInfo Database Record (c) 2023 APA, all rights reserved).


Assuntos
Complexo Nuclear Basolateral da Amígdala , Ratos , Masculino , Animais , Ratos Wistar , Serotonina/farmacologia , Fluoxetina/farmacologia , Ketanserina/farmacologia , 8-Hidroxi-2-(di-n-propilamino)tetralina/farmacologia , Ansiedade , Aprendizagem da Esquiva
14.
Surg Neurol Int ; 13: 113, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35509597

RESUMO

Background: Sphenoid wing meningiomas present close contact with intracranial arteries and have great potential for vascular complications. Here, we describe the case of a patient who presented a medial left giant lesser sphenoid wing meningioma involving the supraclinoid carotid artery. One week after surgery, she developed vasospasm whose treatment using milrinone achieved excellent results. Case Description: This is the case of a 23-year-old female with a large meningioma of the middle third of the lesser wing of the left sphenoid. Furthermore, the patient had symptoms of headache, diplopia, and left amaurosis (Video 1). The lesion involved the supraclinoid left carotid artery, causing significant stenosis of the vessel. The patient underwent surgical treatment without complications. One week after the procedure, she evolved with lowered level of consciousness, complete, and proportionate right hemiparesis and right Babinski's sign. Angiographic study demonstrated significant stenosis of the left supraclinoid artery. After endovascular treatment with milrinone, the patient evolved with immediate improvement of signs and symptoms.Video 1:Surgical procedure. Video is accessible from the portal. Conclusion: Giant meningiomas with vascular involvement involve a higher risk of postoperative vascular complications. Other studies should be carried out to predict these complications and thus develop preventive measures.

15.
Front Neurol ; 13: 1076778, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36712447

RESUMO

Neurosurgical training outside the operating room has become a priority for all neurosurgeons around the world. The exponential increase in the number of publications on training in neurosurgery reflects changes in the environment that future neurosurgeons are expected to work in. In modern practice, patients and medicolegal experts demand objective measures of competence and proficiency in the growing list of techniques available to treat complex neurosurgical conditions. It is important to ensure the myriad of training models available lead to tangible improvements in the operating room. While neuroanatomy textbooks and atlases are continually revised to teach the aspiring surgeon anatomy with a three-dimensional perspective, developing technical skills are integral to the pursuit of excellence in neurosurgery. Parapharsing William Osler, one of the fathers of neurosurgical training, without anatomical knowledge we are lost, but without the experience and skills from practice our journey is yet to begin. It is important to constantly aspire beyond competence to mastery, as we aim to deliver good outcomes for patients in an era of declining case volumes. In this article, we discuss, based on the literature, the most commonly used training models and how they are integrated into the treatment of some surgical brain conditions.

16.
Toxins (Basel) ; 12(9)2020 09 11.
Artigo em Inglês | MEDLINE | ID: mdl-32933013

RESUMO

Pain is a distressful experience that can have a major impact on an individual's quality of life. The need for new and better analgesics has been further intensified in light of the current opioid epidemic. Substances obtained from amphibians have been shown to contain bioactive peptides that exert analgesic effects. The genus Phyllomedusa represents an important source of peptides and bioactive components. The aim of this study was to investigate the antinociceptive effects of the skin secretion of Phyllomedusa rohdei in rodent models of pain. The crude skin extract of P. rohdei was tested in different pain models: acetic acid-induced writhing test (mice), formalin test (rats), Von Frey electronic test for hypernociception induced by PGE2 (rats), and hot plate test (mice). Motor-impairing effects were tested using the rota-rod test. The results showed that the skin extract of P. rohdei exerted antinociceptive effects in all pain models tested. Particularly, the highest dose tested of the skin extract decreased acetic acid-induced writhing by 93%, completely blocked formalin-induced nociception both during the acute and inflammatory phases of the test, PGE2-induced hypernociception by 73% and increased latency to paw withdrawal in the hot plate test by 300%. The effects observed in the hot plate test were reversed by pretreatment with selective µ and κ, but not δ, opioid receptor antagonists, indicating a mechanism of action dependent on µ and κ opioid receptors. The results were not influenced by sedative effects. Further studies remain necessary to reveal the specific compounds involved in the antinociceptive effects of P. rohdei skin extract as a new therapeutic tool in pain management.


Assuntos
Analgésicos/farmacologia , Anuros/metabolismo , Dor Nociceptiva/prevenção & controle , Pele/metabolismo , Analgésicos/metabolismo , Animais , Comportamento Animal/efeitos dos fármacos , Modelos Animais de Doenças , Masculino , Camundongos , Dor Nociceptiva/etiologia , Dor Nociceptiva/metabolismo , Dor Nociceptiva/fisiopatologia , Limiar da Dor/efeitos dos fármacos , Ratos Wistar , Receptores Opioides delta/metabolismo , Receptores Opioides mu/metabolismo , Via Secretória
17.
J Alzheimers Dis ; 73(4): 1525-1539, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31958083

RESUMO

Neuroinflammation has been shown to play a crucial role in the development of Alzheimer's disease (AD) and also has an association with amyloid-ß (Aß) plaques, a hallmark of this disease. Physical exercise has emerged as an alternative treatment for pathological impairment in AD. In light of this evidence, together with the fact that the hippocampus is one of the first structures to be affected in AD, we analyzed hippocampal changes in Aß load, inflammatory responses, and locomotor activity in transgenic APP/PS1 mouse model for AD submitted to a resistance exercise (RE) program. One month after the start of the RE program, the locomotor hyperactivity related to AD behavior was reduced and microglia recruitment was increased, which in turn may have contributed to the decrease in the volume of Aß plaques. In addition, the RE program restored the levels of IL-1α, IL-4, and IL-6 cytokines to control levels. Our study indicates that RE has beneficial effects on the locomotor behavior, amyloid burden, and inflammation of AD pathology and can therefore be used as a therapy to improve the clinical symptoms and neurophysiological alterations in AD. To the best of our knowledge, this is the first study to use a resistance exercise program in transgenic AD model.


Assuntos
Doença de Alzheimer/patologia , Precursor de Proteína beta-Amiloide/genética , Amiloide/metabolismo , Inflamação/patologia , Condicionamento Físico Animal , Presenilina-1/genética , Treinamento Resistido , Doença de Alzheimer/genética , Animais , Carga Corporal (Radioterapia) , Citocinas/metabolismo , Genótipo , Hipocampo/patologia , Humanos , Masculino , Camundongos , Camundongos Transgênicos , Microglia , Atividade Motora
18.
Front Pharmacol ; 10: 211, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30914950

RESUMO

Studies on the abuse potential of modafinil, a psychostimulant-like drug used to treat narcolepsy, are still controversial. While some studies claim no potential for abuse, increasing evidence suggests that modafinil induces abuse-related effects, including rapid-onset behavioral sensitization (i.e., a type of sensitization that develops within hours from the drug priming administration). The rapid-onset sensitization paradigm is a valuable tool to study the neuroplastic changes that occur quickly after drug administration, and shares neuroadaptations with drug abuse in humans. However, the mechanisms involved in the rapid-onset behavioral sensitization induced by modafinil are uncertain. Our aim was to investigate the possible involvement of dopamine D1 and D2 receptors on acute modafinil-induced hyperlocomotion and on the induction and expression of rapid-onset behavioral sensitization induced by modafinil in male Swiss mice. Treatment with the D1 receptor antagonist SCH 23390 or the D2 receptor antagonist sulpiride attenuated the acute modafinil-induced hyperlocomotion in a dose-dependent manner. Pretreatment with either antagonist before the priming injection of modafinil prevented the development of sensitization in response to a modafinil challenge 4 h later. However, only SCH 23390 decreased the expression of modafinil-induced rapid-onset behavioral sensitization. Taken together, the present findings provide evidence of the participation of D1 and D2 receptors on the development of rapid-onset behavioral sensitization to modafinil, and point to a prominent role of D1 receptors on the expression of this phenomenon.

19.
Pharmacol Biochem Behav ; 173: 90-95, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30031027

RESUMO

Opioid addiction is a growing public health problem, being currently considered an epidemic in the United States. Investigating the behavioral effects of opioids and the factors influencing their development becomes of major importance. In animals, the effects of drugs of abuse can be assessed using the behavioral sensitization model, which shares similar neuronal substrates with drug craving in humans. Importantly, novelty plays a critical role on the development of behavioral sensitization. The aim of the present study was to investigate the influence of a new environment on both the induction and expression phases of morphine (Mor)-induced behavioral sensitization in the two-injection protocol. Mice were initially treated with saline, 15 or 30 mg/kg Mor (induction phase), and subsequently challenged 7 days later with 15 mg/Kg Mor (expression phase). Locomotor frequency was evaluated during behavioral sessions, performed as follow: induction session on a novel environment and expression on a familiar open-filed apparatus; induction session on animals' home-cage (familiar environment) and expression session on an unknown open-filed apparatus; both sessions on novel environments; and both sessions on familiar contexts. Mor-induced behavioral sensitization was only observed when animals were exclusively exposed to novelty during the induction phase, not being observed when both the induction and expression sessions were performed on similar (novel or familiar) environments. Our results suggest that the development of behavioral sensitization to Mor depends on the exposure to novelty during the induction phase and absence of novelty during the expression phase, indicating a complex relationship between novelty and Mor-induced behavioral effects.


Assuntos
Comportamento Animal/efeitos dos fármacos , Morfina/farmacologia , Animais , Masculino , Camundongos , Atividade Motora/efeitos dos fármacos
20.
Front Pharmacol ; 7: 420, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27872594

RESUMO

There is substantial controversy about the addictive potential of modafinil, a wake-promoting drug used to treat narcolepsy, proposed as pharmacotherapy for cocaine abuse, and used indiscriminately by healthy individuals due to its positive effects on arousal and cognition. The rapid-onset type of behavioral sensitization (i.e., a type of sensitization that develops within a few hours from the drug priming administration) has been emerged as a valuable tool to study binge-like patterns of drug abuse and the neuroplastic changes that occur quickly after drug administration that ultimately lead to drug abuse. Our aim was to investigate the possible development of rapid-onset behavioral sensitization to modafinil and bidirectional rapid-onset cross-sensitization with cocaine in male Swiss mice. A priming injection of a high dose of modafinil (64 mg/kg) induced rapid-onset behavioral sensitization to challenge injections of modafinil at the doses of 16, 32, and 64 mg/kg, administered 4 h later. Furthermore, rapid-onset cross-sensitization was developed between modafinil and cocaine (64 mg/kg modafinil and 20 mg/kg cocaine), in a bidirectional way. These results were not due to residual levels of modafinil as the behavioral effects of the priming injection of modafinil were no longer present and modafinil plasma concentration was reduced at 4 h post-administration. Taken together, the present findings provide preclinical evidence that modafinil can be reinforcing per se and can enhance the reinforcing effects of stimulants like cocaine within hours after administration.

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