- Neurology - Child Neurology
- Pediatric Epilepsy
Instructor, Neurology & Neurological Sciences
Residency: Boston Children's Hospital (2015) MA
Residency: Boston Children's Hospital (2012) MA
Board Certification: Epilepsy, American Board of Psychiatry and Neurology (2016)
Fellowship: Lucile Packard Children's Hospital (2016) CA
Board Certification: Neurology - Child Neurology, American Board of Psychiatry and Neurology (2015)
Medical Education: Harvard Medical School (2010) MA
Current Research and Scholarly Interests
I am researching the neurobiology underlying cognitive problems in pediatric epilepsy. I am using transcranial magnetic stimulation paired with EMG and EEG to study cortical excitability and plasticity in children with benign epilepsy with centrotemporal spikes (BECTS or Rolandic Epilepsy). I am investigating whether changes in plasticity affect a child's ability to learn.
Transcranial Magnetic Stimulation for BECTS
Benign epilepsy with centrotemporal spikes (BECTS) is the most common pediatric epilepsy syndrome. Affected children typically have a mild seizure disorder, but yet have moderate difficulties with language, learning and attention that impact quality of life more than the seizures. Separate from the seizures, these children have very frequent abnormal activity in their brain known as interictal epileptiform discharges (IEDs, or spikes), which we currently do not treat. These IEDs arise near the motor cortex, a region in the brain that controls movement. In this study, we will use a form of non-invasive brain stimulation called transcranial magnetic stimulation (TMS) to determine the impact of IEDs on brain regions important for language to investigate: (1) if treatment of IEDs could improve language; and (2) if brain stimulation may be a treatment option for children with epilepsy. Participating children will wear electroencephalogram (EEG) caps to measure brain activity. We will use TMS to stimulate the brain region where the IEDs originate to measure how this region is connected to other brain regions. Children will then receive a special form of TMS called repetitive TMS (rTMS) that briefly reduces brain excitability. We will measure if IEDs decrease and if brain connectivity changes after rTMS is applied. We hypothesize that the IEDs cause language problems by increasing connectivity between the motor cortex and language regions. We hypothesize that rTMS will reduce the frequency of IEDs and also reduce connectivity between the motor and language region
Stanford is currently not accepting patients for this trial. For more information, please contact Fiona M Baumer, MD, 650-721-5889.
Lacosamide-Induced Dyskinesia in Children With Intractable Epilepsy.
Journal of child neurology
Lacosamide, an antiepileptic drug prescribed for children with refractory focal epilepsy, is generally well tolerated, with dose-dependent adverse effects. We describe 4 children who developed a movement disorder in conjunction with the initiation and/or uptitration of lacosamide. Three patients developed dyskinesias involving the face or upper extremity whereas the fourth had substantial worsening of chronic facial tics. The patients all had histories suggestive of opercular dysfunction: 3 had seizure semiologies including hypersalivation, facial and upper extremity clonus while the fourth underwent resection of polymicrogyria involving the opercula. Onset, severity, and resolution of dyskinesias correlated with lacosamide dosing. These cases suggest that pediatric patients with dysfunction of the opercular cortex are at increased risk for developing drug-induced dyskinesias on high-dose lacosamide therapy. Practitioners should be aware of this potential side effect and consider weaning lacosamide or video electroencephalography (EEG) for differential diagnosis, particularly in pediatric patients with underlying opercular dysfunction.
View details for DOI 10.1177/0883073820926634
View details for PubMedID 32524876
Management of Infantile Spasms During the COVID-19 Pandemic.
Journal of child neurology
Circumstances of the COVID-19 pandemic have mandated a change to standard management of infantile spasms. On April 6, 2020, the Child Neurology Society issued an online statement of immediate recommendations to streamline diagnosis and treatment of infantile spasms with utilization of telemedicine, outpatient studies, and selection of first-line oral therapies as initial treatment. The rationale for the recommendations and specific guidance including follow-up assessment are provided in this manuscript. These recommendations are indicated as enduring if intended to outlast the pandemic, and limited if intended only for the pandemic health care crisis but may be applicable to future disruptions of health care delivery.
View details for DOI 10.1177/0883073820933739
View details for PubMedID 32576057
- Emerging Applications of Noninvasive Brain Stimulation. Journal of clinical neurophysiology : official publication of the American Electroencephalographic Society 2020; 37 (2): 89
Cortical Excitability, Synaptic Plasticity, and Cognition in Benign Epilepsy With Centrotemporal Spikes: A Pilot TMS-EMG-EEG Study.
Journal of clinical neurophysiology : official publication of the American Electroencephalographic Society
2020; 37 (2): 170–80
Children with benign epilepsy with centrotemporal spikes have rare seizures emerging from the motor cortex, which they outgrow in adolescence, and additionally may have language deficits of unclear etiology. We piloted the use of transcranial magnetic stimulation paired with EMG and EEG (TMS-EMG, TMS-EEG) to test the hypotheses that net cortical excitability decreases with age and that use-dependent plasticity predicts learning.We assessed language and motor learning in 14 right-handed children with benign epilepsy with centrotemporal spikes. We quantified two TMS metrics of left motor cortex excitability: the resting motor threshold (measure of neuronal membrane excitability) and amplitude of the N100-evoked potential (an EEG measure of GABAergic tone). To test plasticity, we applied 1 Hz repetitive TMS to the motor cortex to induce long-term depression-like changes in EMG- and EEG-evoked potentials.Children with benign epilepsy with centrotemporal spikes tolerate TMS; no seizures were provoked. Resting motor threshold decreases with age but is elevated above maximal stimulator output for half the group. N100 amplitude decreases with age after controlling for resting motor threshold. Motor cortex plasticity correlates significantly with language learning and at a trend level with motor learning.Transcranial magnetic stimulation is safe and feasible for children with benign epilepsy with centrotemporal spikes, and TMS-EEG provides more reliable outcome measures than TMS-EMG in this group because many children have unmeasurably high resting motor thresholds. Net cortical excitability decreases with age, and motor cortex plasticity predicts not only motor learning but also language learning, suggesting a mechanism by which motor cortex seizures may interact with language development.
View details for DOI 10.1097/WNP.0000000000000662
View details for PubMedID 32142025
Crisis Standard of Care: Management of Infantile Spasms during COVID-19.
Annals of neurology
The Child Neurology Society collaborated with the Pediatric Epilepsy Research Consortium to issue an online statement April 6, 2020 of immediate recommendations to streamline diagnosis, treatment, and follow up of infantile spasms. The recommendations encourage use of telemedicine, outpatient over inpatient studies, and oral therapies as initial treatment. Each recommendation is earmarked as enduring if intended to outlast the pandemic, and limited if intended only during the duration of the pandemic. This article is protected by copyright. All rights reserved.
View details for DOI 10.1002/ana.25792
View details for PubMedID 32445204
Growing identification of genetic aetiologies for neonatal-onset epilepsies: lessons from the Neonatal Seizure Registry.
Acta paediatrica (Oslo, Norway : 1992)
View details for PubMedID 30399203
Refractory focal epilepsy in a paediatric patient with primary familial brain calcification.
2018; 56: 50–52
Primary familial brain calcification (PFBC), otherwise known as Fahr's disease, is a rare autosomal dominant condition with manifestations of movement disorders, neuropsychiatric symptoms, and epilepsy in a minority of PFBC patients. The clinical presentation of epilepsy in PFBC has not been described in detail. We present a paediatric patient with PFBC and refractory focal epilepsy based on seizure semiology and ictal EEG, but with generalized interictal EEG abnormalities. The patient was found to have a SLC20A2 mutation known to be pathogenic in PFBC, as well as a variant of unknown significance in SCN2A. This case demonstrates that the ictal EEG is important for accurately classifying epilepsy in affected subjects with PFBC. Further, epilepsy in PFBC may be a polygenic disorder.
View details for PubMedID 29448117
Language Dysfunction in Pediatric Epilepsy.
The Journal of pediatrics
2018; 194: 13–21
View details for PubMedID 29241678
Clinical and electrographic features of sunflower syndrome.
2018; 142: 58–63
Sunflower Syndrome describes reflex seizures - typically eyelid myoclonia with or without absence seizures - triggered when patients wave their hands in front of the sun. While valproate has been recognized as the best treatment for photosensitive epilepsy, many clinicians now initially treat with newer medications; the efficacy of these medications in Sunflower Syndrome has not been investigated. We reviewed all cases of Sunflower Syndrome seen at our institution over 15 years to describe the clinical course, electroencephalogram (EEG), and treatment response in these patients.Search of the electronic medical record and EEG database, as well as survey of epilepsy providers at our institution, yielded 13 cases of Sunflower Syndrome between 2002 and 2017. We reviewed the records and EEG tracings.Patients were mostly young females, with an average age of onset of 5.5 years. Seven had intellectual, attentional or academic problems. Self-induced seizures were predominantly eyelid myoclonia ± absences and 6 subjects also had spontaneous seizures. EEG demonstrated a normal background with 3-4 Hz spike waves ± polyspike waves as well as a photoparoxysmal response. Based on both clinical and EEG response, valproate was the most effective treatment for reducing or eliminating seizures and improving the EEG; 9 patients tried valproate and 66% had significant improvement or resolution of seizures. None of the nine patients on levetiracetam or seven patients on lamotrigine monotherapy achieved seizure control, though three patients had improvement with polypharmacy.Valproate monotherapy continues to be the most effective treatment for Sunflower Syndrome and should be considered early. For patients who cannot tolerate valproate, higher doses of lamotrigine or polypharmacy should be considered. Levetiracetam monotherapy, even at high doses, is unlikely to be effective.
View details for PubMedID 29555355
Systemic Manifestations in Pyridox(am)ine Phosphate Oxidase (PNPO) Deficiency
View details for DOI 10.1016/j.pediatrneurol.2017.05.024
Corpus Callosum White Matter Diffusivity Reflects Cumulative Neurological Comorbidity in Tuberous Sclerosis Complex.
Neurological manifestations in Tuberous Sclerosis Complex (TSC) are highly variable. Diffusion tensor imaging (DTI) may reflect the neurological disease burden. We analyzed the association of autism spectrum disorder (ASD), intellectual disability (ID) and epilepsy with callosal DTI metrics in subjects with and without TSC.186 children underwent 3T MRI DTI: 51 with TSC (19 with concurrent ASD), 46 with non-syndromic ASD and 89 healthy controls (HC). Subgroups were based on presence of TSC, ASD, ID, and epilepsy. Density-weighted DTI metrics obtained from tractography of the corpus callosum were fitted using a 2-parameter growth model. We estimated distributions using bootstrapping and calculated half-life and asymptote of the fitted curves.TSC was associated with a lower callosal fractional anisotropy (FA) than ASD, and ASD with a lower FA than HC. ID, epilepsy and ASD diagnosis were each associated with lower FA values, demonstrating additive effects. In TSC, the largest change in FA was related to a comorbid diagnosis of ASD. Mean diffusivity (MD) showed an inverse relationship to FA. Some subgroups were too small for reliable data fitting.Using a cross-disorder approach, this study demonstrates cumulative abnormality of callosal white matter diffusion with increasing neurological comorbidity.
View details for DOI 10.1093/cercor/bhx247
View details for PubMedCentralID PMC6132277
- Quinidine-associated skin discoloration in KCNT1-associated pediatric epilepsy. Neurology 2017; 89 (21): 2212
Diagnosis of adenylosuccinate lyase deficiency by metabolomic profiling in plasma reveals a phenotypic spectrum.
Molecular genetics and metabolism reports
2016; 8: 61-66
Adenylosuccinate lyase (ADSL) deficiency is a rare autosomal recessive neurometabolic disorder that presents with a broad-spectrum of neurological and physiological symptoms. The ADSL gene produces an enzyme with binary molecular roles in de novo purine synthesis and purine nucleotide recycling. The biochemical phenotype of ADSL deficiency, accumulation of SAICAr and succinyladenosine (S-Ado) in biofluids of affected individuals, serves as the traditional target for diagnosis with targeted quantitative urine purine analysis employed as the predominate method of detection. In this study, we report the diagnosis of ADSL deficiency using an alternative method, untargeted metabolomic profiling, an analytical scheme capable of generating semi-quantitative z-score values for over 1000 unique compounds in a single analysis of a specimen. Using this method to analyze plasma, we diagnosed ADSL deficiency in four patients and confirmed these findings with targeted quantitative biochemical analysis and molecular genetic testing. ADSL deficiency is part of a large a group of neurometabolic disorders, with a wide range of severity and sharing a broad differential diagnosis. This phenotypic similarity among these many inborn errors of metabolism (IEMs) has classically stood as a hurdle in their initial diagnosis and subsequent treatment. The findings presented here demonstrate the clinical utility of metabolomic profiling in the diagnosis of ADSL deficiency and highlights the potential of this technology in the diagnostic evaluation of individuals with neurologic phenotypes.
View details for DOI 10.1016/j.ymgmr.2016.07.007
View details for PubMedID 27504266
View details for PubMedCentralID PMC4969260
A 10-Month-Old With Intermittent Hypotonia and Paralysis
2016; 138 (1)
A 10-month-old boy presented with a 1-day history of flaccid quadriplegia and dysconjugate gaze. His history was remarkable for stereotyped episodes of flaccid quadriplegia or hemiplegia, oculomotor abnormalities, and limb or neck posturing, beginning in the first days of life and becoming more frequent and more prolonged over time. The patient was healthy and developmentally normal between episodes. Results of extensive laboratory evaluations, including EEG and brain imaging studies, were negative. The patient's history, diagnostic evaluation, and final diagnosis are reviewed. This case illustrates the importance of a fundamental understanding of neurologic localization in pediatric care and a focused diagnostic approach to an infant with paroxysmal neurologic signs.
View details for DOI 10.1542/peds.2015-1896
View details for Web of Science ID 000378853100004
View details for PubMedID 27252036
Fatal Central Nervous System Disease Following First Infliximab Infusion in a Child With Inflammatory Bowel Disease
2016; 57: 91-94
Infliximab is used in the treatment of inflammatory bowel disease. Previously reported neurological complications include central and peripheral demyelinating disorders and neuropathies occurring months into therapy.A seven-year-old boy diagnosed with ulcerative colitis and primary sclerosing cholangitis received infliximab. Six hours following his uneventful infusion, he awoke with headache and emesis and rapidly became obtunded. Neurological examination revealed minimally reactive pupils and otherwise absent brainstem reflexes. Cranial computed tomography revealed hypodense lesions in the cerebral hemispheres, cerebellum, and pons accompanied by hemorrhage. Magnetic resonance imaging showed diffusion restriction concerning for ischemia with areas of ring enhancement suggestive of inflammation. Vessel imaging was normal, and cerebrospinal fluid and serum studies showed only an extremely elevated level of d-dimer. Echocardiogram showed depressed ventricular function but neither intracardiac shunt nor thrombus. Within four days he met criteria for brain death. Autopsy was refused.This is the first report of a fulminant, fatal central nervous system process to occur after an initial dose of infliximab. The differential diagnosis includes multifocal arterial strokes and a devastating demyelinating process.
View details for DOI 10.1016/j.pediatrneurol.2015.12.017
View details for Web of Science ID 000373522800018
View details for PubMedID 26831951
SCN2A-Related Early-Onset Epileptic Encephalopathy Responsive to Phenobarbital.
Journal of pediatric epilepsy
2016; 5 (1): 42-46
Voltage-gated sodium channels (Nav) are critical regulators of neuronal excitability. Genes for the α-subunits of three sodium channel subtypes-SCN1A, SCN2A, and SCN3A-are all located on chromosome 2q24. A full-term boy with an unremarkable birth history presented at 1 month of age with unusual movements that had started on day of life 2. Exam was notable for lack of visual attention, hypotonia, and hyperreflexia. Electroencephalogram (EEG) showed an invariant burst suppression with multifocal spikes, ictal episodes with bicycling movements associated with buildups of rhythmic activity, and epileptic spasms. Work-up revealed a 1.77-Mb duplication at locus 2q24.3, encompassing the entirety of SCN2A and SCN3A, but not SCN1A. Phenobarbital led to rapid resolution of the clinical seizures and EEG background normalized other than rare sharp waves. Early-onset epileptic encephalopathy (EOEE), with neonatal seizures, burst suppression, and reversibility with phenobarbital, is part of the enlarging spectrum of Nav channelopathies. The delayed diagnosis provided an unusual opportunity to view the early natural history of this disorder and its remarkable responsiveness to barbiturate therapy. The clinical and EEG response to phenobarbital implicates seizures as the cause of the encephalopathy.
View details for PubMedID 27595042
View details for PubMedCentralID PMC5004990
Longitudinal Changes in Diffusion Properties in White Matter Pathways of Children With Tuberous Sclerosis Complex
2015; 52 (6): 615-623
Abnormal white matter development in patients with tuberous sclerosis complex, a multisystem hamartomatous disorder caused by aberrant neural proliferation and axonal maturation, may be associated with poorer neurocognitive outcomes. The purpose of this study is to identify predictors of longitudinal changes in diffusion properties of white matter tracts in patients with tuberous sclerosis complex.Diffusion magnetic resonance imaging was carried out in 17 subjects with tuberous sclerosis complex (mean age, 7.2 ± 4.4 years) with at least two magnetic resonance imaging scans (mean number of days between scans, 419.4 ± 105.4). There were 10 males; 5 of 17 had autism spectrum disorder and 10 of 17 had epilepsy. Regions of interest were placed to delineate the internal capsule/corona radiata, cingulum, and corpus callosum. The outcomes were mean change in apparent diffusion coefficient and fractional anisotropy. Data were analyzed using Pearson's correlation and multiple linear regression analyses.Gender was a significant predictor of mean change in apparent diffusion coefficient in the left internal capsule, right and left cingulum bundles, and corpus callosum and a significant predictor of mean change in fractional anisotropy in the corpus callosum. Epilepsy was a significant predictor of mean change in apparent diffusion coefficient in the left internal capsule. Autism spectrum disorder was not predictive of diffusion changes in any of the studied pathways.Clinical variables, including gender and epilepsy, have an effect on the development of white matter pathways. These variables should be taken into consideration when counseling tuberous sclerosis complex patients and in future imaging studies in this population.
View details for DOI 10.1016/j.pediatrneurol.2015.02.004
View details for Web of Science ID 000355572500007
View details for PubMedID 25817702
View details for PubMedCentralID PMC4442035
- Teaching Video NeuroImages: Nonepileptic myoclonus in a neonate following severe hypoxic-ischemic injury NEUROLOGY 2015; 84 (12): E90-E90
Neuromyelitis Optica in an Adolescent After Bone Marrow Transplantation
2015; 52 (1): 119-124
Central nervous system complications of bone marrow transplant are a common occurrence and the differential diagnosis is quite broad, including opportunistic infections, medications toxicities, graft versus host disease, and other autoimmune processes.We summarize previously reported cases of autoimmune myelitis in post-transplant patients and discuss a 17-year-old boy who presented with seronegative neuromyelitis optica after a bone marrow transplant for acute myeloid leukemia. Our patient had a marked improvement in symptoms after plasmapheresis.Including our patient, there have been at least eight cases of post-transplant autoimmune myelitis presented in the literature, and at least three of these are suspicious for neuromyelitis optica. Several of these patients had poor outcomes with persistent symptoms after the myelitis. Autoimmune processes such as neuromyelitis optica should be carefully considered in patients after transplant as aggressive treatment like early plasmapheresis may improve outcomes.
View details for DOI 10.1016/j.pediatrneurol.2014.07.007
View details for Web of Science ID 000348411800019
View details for PubMedID 25444090
Normative Apparent Diffusion Coefficient Values in the Developing Fetal Brain
AMERICAN JOURNAL OF NEURORADIOLOGY
2009; 30 (9): 1799-1803
Previous studies of diffusion-weighted imaging (DWI) in fetuses are limited. Because of the need for normative data for comparison with young fetuses and preterm neonates with suspected brain abnormalities, we studied apparent diffusion coefficient (ADC) values in a population of singleton, nonsedated, healthy fetuses.DWI was performed in 28 singleton nonsedated fetuses with normal or questionably abnormal results on sonography and normal fetal MR imaging results; 10 fetuses also had a second fetal MR imaging, which included DWI. ADC values in the periatrial white matter (WM), frontal WM, thalamus, basal ganglia, cerebellum, and pons were plotted against gestational age and analyzed with linear regression. We compared mean ADC in different regions using the Tukey Honestly Significant Difference test. We also compared rates of decline in ADC with increasing gestational age across different areas by using the t test with multiple comparisons correction. Neurodevelopmental outcome was assessed.Median gestational age was 24.28 weeks (range, 21-33.43 weeks). Results of all fetal MR imaging examinations were normal, including 1 fetus with a normal variant of a cavum velum interpositum. ADC values were highest in the frontal and periatrial WM and lowest in the thalamus and pons. ADC declined with increasing gestational age in periatrial WM (P = .0003), thalamus (P < .0001), basal ganglia (P = .0035), cerebellum (P < .0001), and pons (P = .024). Frontal WM ADC did not significantly change with gestational age. ADC declined fastest in the cerebellum, followed by the thalamus.Regional differences in nonsedated fetal ADC values and their evolution with gestational age likely reflect differences in brain maturation and are similar to published data in premature neonates.
View details for DOI 10.3174/ajnr.A1661
View details for Web of Science ID 000271031300033
View details for PubMedID 19556350
View details for PubMedCentralID PMC4524324
Fast 3D H-1 MRSI of the Corticospinal Tract in Pediatric Brain
JOURNAL OF MAGNETIC RESONANCE IMAGING
2009; 29 (1): 1-6
To develop a (1)H magnetic resonance spectroscopic imaging (MRSI) sequence that can be used to image infants/children at 3T and by combining it with diffusion tensor imaging (DTI) tractography, extract relevant metabolic information corresponding to the corticospinal tract (CST).A fast 3D MRSI sequence was developed for pediatric neuroimaging at 3T using spiral k-space readout and dual band RF pulses (32 x 32 x 8 cm field of view [FOV], 1 cc iso-resolution, TR/TE = 1500/130, 6:24 minute scan). Using DTI tractography to identify the motor tracts, spectra were extracted from the CSTs and quantified. Initial data from infants/children with suspected motor delay (n = 5) and age-matched controls (n = 3) were collected and N-acetylaspartate (NAA) ratios were quantified.The average signal-to-noise ratio of the NAA peak from the studies was approximately 22. Metabolite profiles were successfully acquired from the CST by using DTI tractography. Decreased NAA ratios in those with motor delay compared to controls of approximately 10% at the CST were observed.A fast and robust 3D MRSI technique targeted for pediatric neuroimaging has been developed. By combining with DTI tractography, metabolic information from the CSTs can be retrieved and estimated. By combining DTI and 3D MRSI, spectral information from various tracts can be obtained and processed.
View details for DOI 10.1002/jmri.21394
View details for Web of Science ID 000262168200001
View details for PubMedID 19097091
View details for PubMedCentralID PMC2832220
A pilot study of antidepressant-induced mania in pediatric bipolar disorder: Characteristics, risk factors, and the serotonin transporter gene
Conference on Pediatric Bipolar Disorder
ELSEVIER SCIENCE INC. 2006: 1005–12
Antidepressant-induced mania (AIM) has been described in bipolar disorder (BD) and has been associated with the short-allele of the serotonin transporter gene (5-HTT). We wished to investigate the frequency of and risk factors for AIM in pediatric patients with or at high risk for BD.Fifty-two children and adolescents (30 with BD and 22 with subthreshold manic symptoms, 15.1 +/- 3.4 years old), all with a parent with BD, were interviewed with their parents for manic/depressive symptoms occurring before and after past antidepressant treatment. The 47 subjects with serotonin reuptake inhibitor (SSRI) exposure were genotyped for the 5-HTT polymorphism.Fifty percent of subjects were AIM+ and 25.5% had new onset of suicidal ideation. The AIM+ and AIM- groups did not differ significantly in relation to allele (p = .36) or genotype (p = .53) frequencies of the 5-HTT polymorphism. The AIM+ subjects were more likely to have more comorbidities (3.2 vs. 2.4; p = .02) and be BD type I (p = .04) than AIM- subjects.Youth with or at high risk for BD may be particularly vulnerable to SSRI AIM and thus should be monitored if given SSRIs. In this preliminary study, we did not find that the 5-HTT polymorphism significantly influenced vulnerability to AIM.
View details for DOI 10.1016/j.biopsych.2006.06.010
View details for PubMedID 16945343
- A pilot study of antidepressant-induced mania in pediatric bipolar disorder: Characteristics, risk factors, and the serotonin transporter gene. Biological Psychiatry 2006; 60 (9): 1005-12
Mercaptoacetate induces feeding through central opioid-mediated mechanisms in rats
2000; 864 (2): 240-251
The endogenous opioid system has been implicated in the mediation of food intake elicited by such regulatory challenges as glucoprivation induced by 2-deoxy-D-glucose (2DG) or food deprivation in rodents. Administration of the free fatty acid oxidation inhibitor, mercaptoacetate (MA), produces a potent short-term increase in feeding in rats, the mechanisms of which have been dissociated from that elicited by 2DG. The present study evaluated whether MA-induced feeding in rats was mediated by the endogenous opioid system through systemic administration of the general opioid antagonist, naltrexone, through central administration of either general, mu, mu(1), kappa(1) or delta opioid antagonists, and through central administration of antisense oligodeoxynucleotide (AS ODN) probes directed against specific exons of either the mu (MOR-1), kappa (KOR-1), kappa(3) (KOR-3/ORL-1) or delta (DOR-1) opioid receptor clones. MA-induced feeding was significantly and dose-dependently reduced by systemic naltrexone (0.005-5 mg/kg); these ingestive effects were quite selective since neither total, ambulatory nor stereotypic activity was affected by either MA itself or MA paired with naltrexone. MA-induced feeding was significantly reduced by central pretreatment with either naltrexone (0.1-20 microgram) or mu-selective (beta-funaltrexamine, 0.1-20 microgram), mu(1)-selective (naloxonazine, 1-20 microgram), kappa(1)-selective (nor-binaltorphamine, 0.1-20 microgram), or delta-selective (naltrindole, 1-20 microgram) opioid receptor antagonists. MA-induced feeding was significantly reduced by AS ODN probes directed against either exons 1, 2 or 3, but not exon 4 of the MOR-1 clone, exon 3, but not exons 1 or 2 of the KOR-1 clone, exons 1 or 2, but not exon 3 of the KOR-3/ORL-1 clone, and exon 1, but not exons 2 or 3 of the DOR-1 clone. These data are discussed in terms of opioid mediation of ingestive responses related to fat, and in terms of potential central sites of action at which lipoprivic ingestive responses might act.
View details for Web of Science ID 000087003000009
View details for PubMedID 10802031