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Article ; Online: Defining Substance Use Disorders: The Need for Peripheral Biomarkers.

Bough, Kristopher J / Pollock, Jonathan D

2018 Volume 24, Issue 2, Page(s) 109–120

Abstract: Addiction is a brain disease, and current diagnostic criteria for substance use disorders (SUDs) are qualitative. Nevertheless, scientific advances are beginning to characterize neurobiological domains. Combining multiple units of measure may provide an ... ...

Abstract	Addiction is a brain disease, and current diagnostic criteria for substance use disorders (SUDs) are qualitative. Nevertheless, scientific advances are beginning to characterize neurobiological domains. Combining multiple units of measure may provide an opportunity to deconstruct the heterogeneities of a SUD and define endophenotypes by using peripheral biospecimens. There are several recent examples of potential biomarker types that can be examined, together with their categorical applications for SUDs. We propose that, in conjunction with rapidly advancing statistical and mathematical modeling techniques, there is now a unique opportunity for the discovery of composite biomarkers within specific domains of addiction; these may lay the foundation for future biomarker qualification, with important implications for drug development and medical care.
MeSH term(s)	Biomarkers/metabolism ; Humans ; Needs Assessment ; Substance-Related Disorders/diagnosis ; Substance-Related Disorders/metabolism
Chemical Substances	Biomarkers
Language	English
Publishing date	2018-01-25
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2036490-8
ISSN	1471-499X ; 1471-4914
ISSN (online)	1471-499X
ISSN	1471-4914
DOI	10.1016/j.molmed.2017.12.009
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Article ; Online: Energy metabolism as part of the anticonvulsant mechanism of the ketogenic diet.

Bough, Kristopher

Epilepsia

2008 Volume 49 Suppl 8, Page(s) 91–93

Abstract: The efficacy of the ketogenic diet (KD) develops gradually over a period of 1-3 weeks, suggesting that adaptive changes in gene expression are involved in its anticonvulsant effects. Previously, microarrays were employed to define patterns of gene ... ...

Abstract	The efficacy of the ketogenic diet (KD) develops gradually over a period of 1-3 weeks, suggesting that adaptive changes in gene expression are involved in its anticonvulsant effects. Previously, microarrays were employed to define patterns of gene expression in the hippocampus of rats maintained on either a KD or a control diet for 3 weeks. The density of mitochondria in hippocampal tissue was assessed by electron microscopy. Levels of selected energy metabolites, enzyme activities, and the effect of low glucose on synaptic transmission were also investigated in hippocampal tissue taken from either KD- or control-fed animals. We found a coordinated up-regulation of transcripts encoding energy metabolism enzymes and a dramatic 46% increase in the density of mitochondria observed in neuronal processes. These changes were accompanied by an increased phosphocreatine (PCr):creatine (Cr) energy-store ratio. Consistent with heightened energy reserves, hippocampal synaptic transmission in KD-fed animals was maintained approximately 50% longer compared to controls after exposure to a mild metabolic stressor. Taken together, several lines of evidence indicate that the KD enhances energy production in the brain. As a consequence, brain tissue appears to become more resistant to metabolic stress. It is proposed...that the observed KD-induced enhancements in energy metabolism help to compensate for the metabolic deficits exhibited (interictally) within epileptic foci and transient failures of gamma-aminobutyric acid (GABA) ergic inhibition, which would otherwise favor the initiation and propagation of seizure activity.
MeSH term(s)	Animals ; Anticonvulsants/metabolism ; Anticonvulsants/pharmacology ; Diet, Ketogenic ; Energy Metabolism/physiology ; Epilepsy/diet therapy ; Gene Expression ; Hippocampus/physiology ; Humans ; Rats ; Synaptic Transmission/physiology
Chemical Substances	Anticonvulsants
Language	English
Publishing date	2008-11-25
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	216382-2
ISSN	1528-1167 ; 0013-9580
ISSN (online)	1528-1167
ISSN	0013-9580
DOI	10.1111/j.1528-1167.2008.01846.x
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Article ; Online: National Institutes of Health (NIH) Executive Meeting Summary: Developing Medical Countermeasures to Rescue Opioid-Induced Respiratory Depression (a Trans-Agency Scientific Meeting)-August 6/7, 2019.

Yeung, David T / Bough, Kristopher J / Harper, Jill R / Platoff, Gennady E

Journal of medical toxicology : official journal of the American College of Medical Toxicology

2019 Volume 16, Issue 1, Page(s) 87–105

Abstract: On August 6th, 2019, a two-day trans-agency scientific meeting was convened by the United States (U.S.) National Institute of Allergy and Infectious Diseases (NIAID/NIH) on the research and development of medical countermeasures (MCMs) and treatment ... ...

Abstract	On August 6th, 2019, a two-day trans-agency scientific meeting was convened by the United States (U.S.) National Institute of Allergy and Infectious Diseases (NIAID/NIH) on the research and development of medical countermeasures (MCMs) and treatment strategies to mitigate synthetic opioid-induced toxicities. This trans-agency meeting was an initiative of the Chemical Countermeasures Research Program (CCRP) and organized by the NIAID in collaboration with the National Institute of Drug Abuse (NIDA), the Biomedical Advanced Research and Development Authority (BARDA), the Food and Drug Administration (FDA), and the Defense Threat Reduction Agency (DTRA). The CCRP is part of the larger NIH biodefense research program coordinated by NIAID, which also includes MCM research and development programs against biological, radiological, and nuclear threats. Its overarching goal is to integrate cutting-edge research and technological advances in science and medicine to enhance the nation's medical response capabilities during and after a public health emergency involving the deliberate or accidental release of toxic chemicals. The potential of a mass casualty public health event involving synthetic opioids is a rapidly growing concern. As such, the overall goals of this trans-agency meeting are to better understand opioid-induced toxicities and advance the development of MCMs to mitigate and reverse opioid-induced respiratory depression (OIRD) to prevent consequential mortality. The primary objectives of the meeting were (1) highlight the latest research on mechanisms of OIRD and related toxicities, animal models, diagnostics, delivery technologies, and emerging new treatment options to prevent lethality; (2) identify current knowledge gaps to advance medical countermeasure development; (3) hear from the U.S. FDA on regulatory considerations to support new technology and treatment approaches; and (4) provide a forum for networking and collaborative partnerships. To accomplish this, a diverse group of almost 200 US domestic and international subject matter experts spanning fundamental and translational research from academia, industry, and government came together in-person to share their collective expertise and experience in this important field. This report briefly summarizes the information presented throughout the meeting, which was also webcast live in its entirety to registered remote attendees.
MeSH term(s)	Analgesics, Opioid/adverse effects ; Analgesics, Opioid/chemical synthesis ; Animals ; Biomedical Research ; Chemical Terrorism ; Disease Models, Animal ; Humans ; Medical Countermeasures ; National Institute of Allergy and Infectious Diseases (U.S.) ; Opioid Epidemic/mortality ; Opioid-Related Disorders/diagnosis ; Opioid-Related Disorders/mortality ; Opioid-Related Disorders/therapy ; Public-Private Sector Partnerships ; Respiration/drug effects ; Respiratory Insufficiency/chemically induced ; Respiratory Insufficiency/diagnosis ; Respiratory Insufficiency/mortality ; Respiratory Insufficiency/therapy ; Stakeholder Participation ; United States
Chemical Substances	Analgesics, Opioid
Language	English
Publishing date	2019-12-18
Publishing country	United States
Document type	Congress ; Research Support, N.I.H., Extramural
ZDB-ID	2435016-3
ISSN	1937-6995 ; 1556-9039
ISSN (online)	1937-6995
ISSN	1556-9039
DOI	10.1007/s13181-019-00750-x
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Article: Anticonvulsant mechanisms of the ketogenic diet.

Bough, Kristopher J / Rho, Jong M

Epilepsia

2007 Volume 48, Issue 1, Page(s) 43–58

Abstract: The ketogenic diet (KD) is a broadly effective treatment for medically refractory epilepsy. Despite nearly a century of use, the mechanisms underlying its clinical efficacy remain unknown. In this review, we present one intersecting view of how the KD ... ...

Abstract	The ketogenic diet (KD) is a broadly effective treatment for medically refractory epilepsy. Despite nearly a century of use, the mechanisms underlying its clinical efficacy remain unknown. In this review, we present one intersecting view of how the KD may exert its anticonvulsant activity against the backdrop of several seemingly disparate mechanistic theories. We summarize key insights gleaned from experimental and clinical studies of the KD, and focus particular attention on the role that ketone bodies, fatty acids, and limited glucose may play in seizure control. Chronic ketosis is anticipated to modify the tricarboxcylic acid cycle to increase GABA synthesis in brain, limit reactive oxygen species (ROS) generation, and boost energy production in brain tissue. Among several direct neuro-inhibitory actions, polyunsaturated fatty acids increased after KD induce the expression of neuronal uncoupling proteins (UCPs), a collective up-regulation of numerous energy metabolism genes, and mitochondrial biogenesis. These effects further limit ROS generation and increase energy production. As a result of limited glucose and enhanced oxidative phosphorylation, reduced glycolytic flux is hypothesized to activate metabolic K(ATP) channels and hyperpolarize neurons and/or glia. Although it is unlikely that a single mechanism, however well substantiated, will explain all of the diet's clinical benefits, these diverse, coordinated changes seem poised to stabilize synaptic function and increase the resistance to seizures throughout the brain.
MeSH term(s)	Diet, Carbohydrate-Restricted ; Dietary Carbohydrates/administration & dosage ; Dietary Carbohydrates/metabolism ; Dietary Fats/administration & dosage ; Dietary Fats/metabolism ; Dietary Proteins/administration & dosage ; Dietary Proteins/metabolism ; Energy Metabolism ; Epilepsy/diet therapy ; Epilepsy/metabolism ; Humans ; Ketone Bodies/biosynthesis ; Ketone Bodies/metabolism ; Ketosis/metabolism ; Reactive Oxygen Species/metabolism ; Treatment Outcome
Chemical Substances	Dietary Carbohydrates ; Dietary Fats ; Dietary Proteins ; Ketone Bodies ; Reactive Oxygen Species
Language	English
Publishing date	2007-01
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	216382-2
ISSN	1528-1167 ; 0013-9580
ISSN (online)	1528-1167
ISSN	0013-9580
DOI	10.1111/j.1528-1167.2007.00915.x
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Article: The ketogenic diet for the treatment of epilepsy: a challenge for nutritional neuroscientists.

Stafstrom, Carl E / Bough, Kristopher J

Nutritional neuroscience

2003 Volume 6, Issue 2, Page(s) 67–79

Abstract: The ketogenic diet (KD) is a high-fat, low-carbohydrate, adequate-protein diet that has been used for more than eight decades for the treatment of refractory epilepsy in children. Despite this long history, the mechanisms by which the KD exerts its anti- ... ...

Abstract	The ketogenic diet (KD) is a high-fat, low-carbohydrate, adequate-protein diet that has been used for more than eight decades for the treatment of refractory epilepsy in children. Despite this long history, the mechanisms by which the KD exerts its anti-seizure action are not fully understood. Questions remain regarding several aspects of KD action, including its effects on brain biochemistry and energetics, neuronal membrane function and cellular network behavior. With the explosion of the KD use in the last 10 years, it is now imperative that we understand these factors in greater detail, in order to optimize the formulation, administration and fine-tuning of the diet. This review discusses what is known and what remains to be learned about the KD, with emphasis on clinical questions that can be approached in the laboratory. We encourage scientists with a primary interest in nutritional neuroscience to join with those of us in the epilepsy research community to address these urgent questions, for the benefit of children ravaged by intractable seizures.
MeSH term(s)	Age Factors ; Animals ; Brain/metabolism ; Child, Preschool ; Cognition ; Dietary Carbohydrates/administration & dosage ; Dietary Fats/administration & dosage ; Dietary Proteins/administration & dosage ; Energy Intake ; Epilepsy/diet therapy ; Humans ; Infant ; Ketone Bodies/metabolism ; Nutritional Physiological Phenomena ; Treatment Outcome
Chemical Substances	Dietary Carbohydrates ; Dietary Fats ; Dietary Proteins ; Ketone Bodies
Language	English
Publishing date	2003-04
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	1447449-9
ISSN	1476-8305 ; 1028-415X
ISSN (online)	1476-8305
ISSN	1028-415X
DOI	10.1080/1028415031000084427
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Article: Path Analysis Shows That Increasing Ketogenic Ratio, but Not β-Hydroxybutyrate, Elevates Seizure Threshold in the Rat

Bough, Kristopher J. / Chen, Ru San / Eagles, Douglas A.

Developmental Neuroscience

2011 Volume 21, Issue 3-5, Page(s) 400–406

Abstract: Previous work has identified several criteria that may be important in determining the efficacy of the ketogenic diet as a treatment for intractable epilepsy in children. The present study was designed to investigate the influence of four major variables ...

Institution	Departments of Biology and Academic and Information Technology Services, Washington, D.C., USA
Abstract	Previous work has identified several criteria that may be important in determining the efficacy of the ketogenic diet as a treatment for intractable epilepsy in children. The present study was designed to investigate the influence of four major variables on seizure threshold, i.e. ketogenic ratio, body weight, age at diet onset and β-hydroxybutyrate in rats. Path analysis was used to statistically model and quantify the causal relationships among variables. Results indicate that seizure threshold was significantly elevated with increasing ketogenic ratios (i.e. more fats vs. carbohydrates and proteins) and decreasing weight. Conversely, age at diet onset and plasma levels of β-OHB showed no causal relation to seizure resistance. These results suggest that the efficacy of the ketogenic diet is independent of the level of ketonemia but is markedly influenced by diet and growth.
Keywords	Ketogenic diet ; Epilepsy ; Seizure ; Pentylenetetrazole ; β-Hydroxybutyrate ; Rat
Language	English
Publishing date	2011-04-29
Publisher	S. Karger AG
Publishing place	Basel, Switzerland
Document type	Article
Note	Paper
ZDB-ID	556887-0
ISBN	978-3-8055-6925-5 ; 978-3-318-00471-7 ; 3-8055-6925-4 ; 3-318-00471-5
ISSN	1421-9859 ; 0378-5866
ISSN (online)	1421-9859
ISSN	0378-5866
DOI	10.1159/000017390
Database	Karger publisher's database

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Article: Medial perforant path inhibition mediated by mGluR7 is reduced after status epilepticus.

Bough, Kristopher J / Mott, David D / Dingledine, Raymond J

Journal of neurophysiology

2004 Volume 92, Issue 3, Page(s) 1549–1557

Abstract: Metabotropic glutamate receptor (mGluR)-mediated inhibition within the dentate gyrus is altered after epilepsy. Whether these changes occur during the developmental period of the disease (i.e., the latent period) has not yet been investigated. Field ... ...

Abstract	Metabotropic glutamate receptor (mGluR)-mediated inhibition within the dentate gyrus is altered after epilepsy. Whether these changes occur during the developmental period of the disease (i.e., the latent period) has not yet been investigated. Field excitatory postsynaptic potentials (fEPSPs) were recorded in the lateral (LPP) and medial perforant path (MPP) simultaneously in adult mouse hippocampal slices 3-9 days after pilocarpine (PILO)-induced status epilepticus. Genetically manipulated mice (mGluR8 knockout and mGluR4/8 double knockout) and pharmacologically selective agonists were used to identify specific mGluR subtypes affected after PILO. Pharmacological activation of mGluR7 by L-AP4 in both wild-type and mGluR4/8 double knockout mice selectively reduced fEPSPs in the MPP, but not LPP, and this level of inhibition was significantly reduced 3-9 days after PILO-induced SE. Activation of mGluR2/3 reversibly depressed the fEPSP slopes in both the MPP and LPP, but no alterations were noted after PILO. mGluR8 activation selectively inhibited evoked responses in the LPP, but not in the MPP, and this level of inhibition did not change after PILO treatment. These data suggest that reduced presynaptic inhibition mediated by mGluR7, but not mGluR2/3 or mGluR8, may play a role during the latent period in generating hyperexcitability in the dentate and thereby contribute to epileptogenesis.
MeSH term(s)	Animals ; Excitatory Amino Acid Agonists/pharmacology ; Male ; Mice ; Mice, Knockout ; Neural Inhibition/drug effects ; Neural Inhibition/physiology ; Perforant Pathway/drug effects ; Perforant Pathway/physiology ; Receptors, Metabotropic Glutamate/agonists ; Receptors, Metabotropic Glutamate/metabolism ; Status Epilepticus/metabolism ; Synaptic Transmission/drug effects ; Synaptic Transmission/physiology
Chemical Substances	Excitatory Amino Acid Agonists ; Receptors, Metabotropic Glutamate ; metabotropic glutamate receptor 7
Language	English
Publishing date	2004-09
Publishing country	United States
Document type	Comparative Study ; Journal Article ; Research Support, U.S. Gov't, P.H.S.
ZDB-ID	80161-6
ISSN	1522-1598 ; 0022-3077
ISSN (online)	1522-1598
ISSN	0022-3077
DOI	10.1152/jn.00315.2004
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Article: Calorie restriction and ketogenic diet diminish neuronal excitability in rat dentate gyrus in vivo.

Bough, Kristopher J / Schwartzkroin, Philip A / Rho, Jong M

Epilepsia

2002 Volume 44, Issue 6, Page(s) 752–760

Abstract: Purpose: The ketogenic diet (KD) is an effective treatment for intractable epilepsy. However, little is known about its underlying mechanisms.: Methods: In this study, in vivo extracellular field responses to angular bundle stimulation were recorded ... ...

Abstract	Purpose: The ketogenic diet (KD) is an effective treatment for intractable epilepsy. However, little is known about its underlying mechanisms. Methods: In this study, in vivo extracellular field responses to angular bundle stimulation were recorded in the dentate gyrus of Sprague-Dawley rats fed one of three diets: ketogenic calorie-restricted (KCR), normal calorie-restricted (NCR), or normal ad libitum (NAL). Input/output curves and paired-pulse relations were used to assess network excitability. A maximal dentate activation (MDA) protocol was used to measure electrographic seizure threshold and duration. Results: Animals fed calorie-restricted (CR) diets exhibited greater paired-pulse inhibition, an elevated MDA threshold, and an absence of spreading depression-like events compared with ad libitum-fed controls. In the MDA model of epileptogenesis, the rate of increase in electrographic seizure duration after repeated stimuli was markedly reduced in KCR-fed animals compared with NCR- and NAL-fed controls. Conclusions: These data suggest that CR, by itself, can be anticonvulsant, and treatment with a KCR diet may be both anticonvulsant and antiepileptogenic.
MeSH term(s)	Animals ; Caloric Restriction ; Dentate Gyrus/metabolism ; Dentate Gyrus/physiology ; Dietary Carbohydrates/administration & dosage ; Dietary Carbohydrates/metabolism ; Dietary Fats/administration & dosage ; Dietary Fats/metabolism ; Disease Models, Animal ; Electric Stimulation ; Electrodes, Implanted ; Electrophysiology ; Epilepsy/diet therapy ; Epilepsy/metabolism ; Epilepsy/prevention & control ; Food, Formulated ; Humans ; Ketone Bodies/blood ; Ketone Bodies/metabolism ; Ketosis/chemically induced ; Ketosis/metabolism ; Kindling, Neurologic/metabolism ; Kindling, Neurologic/physiology ; Male ; Rats ; Rats, Sprague-Dawley
Chemical Substances	Dietary Carbohydrates ; Dietary Fats ; Ketone Bodies
Language	English
Publishing date	2002-09-04
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, P.H.S.
ZDB-ID	216382-2
ISSN	1528-1167 ; 0013-9580
ISSN (online)	1528-1167
ISSN	0013-9580
DOI	10.1046/j.1528-1157.2003.55502.x
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Article ; Online: Biomarkers for the development of new medications for cocaine dependence.

Bough, Kristopher J / Amur, Shashi / Lao, Guifang / Hemby, Scott E / Tannu, Nilesh S / Kampman, Kyle M / Schmitz, Joy M / Martinez, Diana / Merchant, Kalpana M / Green, Charles / Sharma, Jyoti / Dougherty, Anne H / Moeller, F Gerard

Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology

2013 Volume 39, Issue 1, Page(s) 202–219

Abstract: There has been significant progress in personalized drug development. In large part, this has taken place in the oncology field and been due to the ability of researchers/clinicians to discover and develop novel drug development tools (DDTs), such as ... ...

Abstract	There has been significant progress in personalized drug development. In large part, this has taken place in the oncology field and been due to the ability of researchers/clinicians to discover and develop novel drug development tools (DDTs), such as biomarkers. In cancer treatment research, biomarkers have permitted a more accurate pathophysiological characterization of an individual patient, and have enabled practitioners to target mechanistically the right drug, to the right patient, at the right time. Similar to cancer, patients with substance use disorders (SUDs) present clinically with heterogeneous symptomatology and respond variably to therapeutic interventions. If comparable biomarkers could be identified and developed for SUDs, significant diagnostic and therapeutic advances could be made. In this review, we highlight current opportunities and difficulties pertaining to the identification and development of biomarkers for SUDs. We focus on cocaine dependence as an example. Putative diagnostic, pharmacodynamic (PD), and predictive biomarkers for cocaine dependence are discussed across a range of methodological approaches. A possible cocaine-dependent clinical outcome assessment (COA)--another type of defined DDT--is also discussed. At present, biomarkers for cocaine dependence are in their infancy. Much additional research will be needed to identify, validate, and qualify these putative tools prior to their potential use for medications development and/or application to clinical practice. However, with a large unmet medical need and an estimated market size of several hundred million dollars per year, if developed, biomarkers for cocaine dependence will hold tremendous value to both industry and public health.
MeSH term(s)	Animals ; Biomarkers, Pharmacological/metabolism ; Cardiovascular System/metabolism ; Cocaine-Related Disorders/diagnosis ; Cocaine-Related Disorders/drug therapy ; Cocaine-Related Disorders/metabolism ; Drug Discovery/methods ; Humans ; Neuroimaging ; Substance-Related Disorders/drug therapy ; Substance-Related Disorders/metabolism ; Treatment Outcome
Chemical Substances	Biomarkers, Pharmacological
Language	English
Publishing date	2013-08-27
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	639471-1
ISSN	1740-634X ; 0893-133X
ISSN (online)	1740-634X
ISSN	0893-133X
DOI	10.1038/npp.2013.210
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Article: Metabotropic glutamate receptors modulate feedback inhibition in a developmentally regulated manner in rat dentate gyrus.

Doherty, James J / Alagarsamy, Sudar / Bough, Kristopher J / Conn, P Jeffrey / Dingledine, Raymond / Mott, David D

The Journal of physiology

2004 Volume 561, Issue Pt 2, Page(s) 395–401

Abstract: We investigated group II metabotropic glutamate receptor (mGluR) modulation of glutamatergic input onto hilar-border interneurones and its regulation of feedback inhibition in the dentate gyrus. Selective activation of group II mGluRs with (2S,2'R,3'R)-2- ...

Abstract	We investigated group II metabotropic glutamate receptor (mGluR) modulation of glutamatergic input onto hilar-border interneurones and its regulation of feedback inhibition in the dentate gyrus. Selective activation of group II mGluRs with (2S,2'R,3'R)-2-(2',3'-dicarboxycyclopropyl)glycine (DCG-IV) depressed mossy fibre (MF)-evoked excitatory drive to these interneurones with significantly greater depression in juvenile than adult rats. During 20 Hz MF stimulus trains, EPSCs became depressed. Depression during the early, but not later part of the train was significantly greater in juvenile than adult rats and was blocked by the mGluR antagonist (2S)-2-amino-2-[(1S,2S)-2-carboxycycloprop-1-yl]-3-(xanth-9-yl) propanoic acid (LY341495). In dentate granule cells from juvenile rats polysynaptic feedback IPSCs, but not monosynaptic IPSCs, were strongly suppressed by DCG-IV. DCG-IV also suppressed feedback inhibition of perforant path-evoked population spikes. In contrast, in adult animals DCG-IV did not significantly depress feedback inhibition. During 20 Hz stimulus trains in juvenile animals the summation of polysynaptic, but not monosynaptic IPSCs was suppressed by synaptically activated group II mGluRs. Blockade of these mGluRs with LY341495 significantly increased the area and duration of the summated IPSC, causing greater feedback inhibition of granule cell firing. In contrast, in adult animals LY341495 did not alter feedback inhibition following the stimulus train. These findings indicate that group II mGluRs modulate excitatory drive to interneurones in a developmentally regulated manner and thereby modulate feedback inhibition in the dentate gyrus.
MeSH term(s)	Amino Acids/pharmacology ; Animals ; Dentate Gyrus/growth & development ; Excitatory Postsynaptic Potentials/physiology ; Feedback, Physiological/physiology ; Neural Inhibition/physiology ; Rats ; Rats, Sprague-Dawley ; Receptors, Metabotropic Glutamate/antagonists & inhibitors ; Receptors, Metabotropic Glutamate/physiology ; Xanthenes/pharmacology
Chemical Substances	Amino Acids ; LY 341495 ; Receptors, Metabotropic Glutamate ; Xanthenes
Language	English
Publishing date	2004-12-01
Publishing country	England
Document type	Comparative Study ; Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, P.H.S.
ZDB-ID	3115-x
ISSN	1469-7793 ; 0022-3751
ISSN (online)	1469-7793
ISSN	0022-3751
DOI	10.1113/jphysiol.2004.074930
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