Acute gabapentin administration in healthy adults. A double-blind placebo-controlled study using transcranial magnetic stimulation and 7T 1H-MRS
Gamma-aminobutyric acid (GABA) and glutamate are the primary neurotransmitters responsible for modulating excitatory and inhibitory signalling within the human brain. Dysfunctional GABAergic and glutamatergic signalling has been identified as a key factor in a range of neuropsychiatric conditions; h...
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| Language: | English |
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Elsevier
2021-03-01
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| Series: | NeuroImage: Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2666956021000015 |
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| author | Katherine Dyke Sophia E. Pépés Ben Babourina-Brooks Chen Chen Soyoung Kim Hilmar P. Sigurdsson Amelia Draper Masud Husain Parashkev Nachev Penny Gowland Peter G. Morris Stephen R. Jackson |
| author_facet | Katherine Dyke Sophia E. Pépés Ben Babourina-Brooks Chen Chen Soyoung Kim Hilmar P. Sigurdsson Amelia Draper Masud Husain Parashkev Nachev Penny Gowland Peter G. Morris Stephen R. Jackson |
| author_sort | Katherine Dyke |
| collection | DOAJ |
| description | Gamma-aminobutyric acid (GABA) and glutamate are the primary neurotransmitters responsible for modulating excitatory and inhibitory signalling within the human brain. Dysfunctional GABAergic and glutamatergic signalling has been identified as a key factor in a range of neuropsychiatric conditions; hence measurement and modulation of these neurometabolites is important for improving our understanding of neuropsychiatric conditions and treatment options. Gabapentin (GBP) is one of several drugs developed to increase GABA levels and is routinely prescribed for conditions such as epilepsy and neuralgia. While animal and human studies indicate that GBP can elevate GABA levels, its exact mechanisms of action are not fully understood, although animal studies indicate that GBP does not have a direct effect upon GABAergic receptors.To investigate the impact of acute GBP administration in the human motor system we used two complimentary approaches – transcranial magnetic stimulation (TMS) and magnetic resonance spectroscopy (MRS). MRS and TMS measures of GABA have repeatedly been found to be uncorrelated and are likely to reflect different pools of synaptic and extra synaptic GABA, hence, measuring both within the same participants allows for an in-depth assessment of GBP effects.Despite significantly increased ratings of fatigue and tiredness within the GBP group, we failed to find any statistically significant changes in our MRS or TMS measures of GABA. Measures of MRS Glutamate (glu) and glutamine (gln) were also not affected by the administration of GBP. These findings are important as they run counter to previous work, and suggest that the effect of an acute dose of GBP is likely to be subject to substantial individual variation, with timing of measures particularly likely to impact observed effects. These findings have implications for the use of acute GBP dosing as a means to explore GABAergic function in health and disease. |
| format | Article |
| id | doaj-art-09d5ed9719924dd2837e4b72ac0ec9de |
| institution | OA Journals |
| issn | 2666-9560 |
| language | English |
| publishDate | 2021-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | NeuroImage: Reports |
| spelling | doaj-art-09d5ed9719924dd2837e4b72ac0ec9de2025-08-20T01:59:17ZengElsevierNeuroImage: Reports2666-95602021-03-011110000310.1016/j.ynirp.2021.100003Acute gabapentin administration in healthy adults. A double-blind placebo-controlled study using transcranial magnetic stimulation and 7T 1H-MRSKatherine Dyke0Sophia E. Pépés1Ben Babourina-Brooks2Chen Chen3Soyoung Kim4Hilmar P. Sigurdsson5Amelia Draper6Masud Husain7Parashkev Nachev8Penny Gowland9Peter G. Morris10Stephen R. Jackson11School of Psychology, University of Nottingham, UK; Corresponding author.School of Psychology, University of Nottingham, UKSir Peter Mansfield Imaging Centre, University of Nottingham, UKSir Peter Mansfield Imaging Centre, University of Nottingham, UKSchool of Psychology, University of Nottingham, UK; Institute of Mental Health, School of Medicine, University of Nottingham, UKSchool of Psychology, University of Nottingham, UKSchool of Psychology, University of Nottingham, UKNuffield Department of Clinical Neuroscience, University of Oxford, UKInstitute of Cognitive Neuroscience, University College London, UKSir Peter Mansfield Imaging Centre, University of Nottingham, UKSir Peter Mansfield Imaging Centre, University of Nottingham, UKSchool of Psychology, University of Nottingham, UK; Sir Peter Mansfield Imaging Centre, University of Nottingham, UK; Institute of Mental Health, School of Medicine, University of Nottingham, UKGamma-aminobutyric acid (GABA) and glutamate are the primary neurotransmitters responsible for modulating excitatory and inhibitory signalling within the human brain. Dysfunctional GABAergic and glutamatergic signalling has been identified as a key factor in a range of neuropsychiatric conditions; hence measurement and modulation of these neurometabolites is important for improving our understanding of neuropsychiatric conditions and treatment options. Gabapentin (GBP) is one of several drugs developed to increase GABA levels and is routinely prescribed for conditions such as epilepsy and neuralgia. While animal and human studies indicate that GBP can elevate GABA levels, its exact mechanisms of action are not fully understood, although animal studies indicate that GBP does not have a direct effect upon GABAergic receptors.To investigate the impact of acute GBP administration in the human motor system we used two complimentary approaches – transcranial magnetic stimulation (TMS) and magnetic resonance spectroscopy (MRS). MRS and TMS measures of GABA have repeatedly been found to be uncorrelated and are likely to reflect different pools of synaptic and extra synaptic GABA, hence, measuring both within the same participants allows for an in-depth assessment of GBP effects.Despite significantly increased ratings of fatigue and tiredness within the GBP group, we failed to find any statistically significant changes in our MRS or TMS measures of GABA. Measures of MRS Glutamate (glu) and glutamine (gln) were also not affected by the administration of GBP. These findings are important as they run counter to previous work, and suggest that the effect of an acute dose of GBP is likely to be subject to substantial individual variation, with timing of measures particularly likely to impact observed effects. These findings have implications for the use of acute GBP dosing as a means to explore GABAergic function in health and disease.http://www.sciencedirect.com/science/article/pii/S2666956021000015Gamma-aminobutyric acid (GABA)Glutamate (Glu)Glutamine (Gln)Magnetic resonance spectroscopy (MRS)Transcranial magnetic stimulation (TMS)Short interval intracortical inhibition (SICI) |
| spellingShingle | Katherine Dyke Sophia E. Pépés Ben Babourina-Brooks Chen Chen Soyoung Kim Hilmar P. Sigurdsson Amelia Draper Masud Husain Parashkev Nachev Penny Gowland Peter G. Morris Stephen R. Jackson Acute gabapentin administration in healthy adults. A double-blind placebo-controlled study using transcranial magnetic stimulation and 7T 1H-MRS NeuroImage: Reports Gamma-aminobutyric acid (GABA) Glutamate (Glu) Glutamine (Gln) Magnetic resonance spectroscopy (MRS) Transcranial magnetic stimulation (TMS) Short interval intracortical inhibition (SICI) |
| title | Acute gabapentin administration in healthy adults. A double-blind placebo-controlled study using transcranial magnetic stimulation and 7T 1H-MRS |
| title_full | Acute gabapentin administration in healthy adults. A double-blind placebo-controlled study using transcranial magnetic stimulation and 7T 1H-MRS |
| title_fullStr | Acute gabapentin administration in healthy adults. A double-blind placebo-controlled study using transcranial magnetic stimulation and 7T 1H-MRS |
| title_full_unstemmed | Acute gabapentin administration in healthy adults. A double-blind placebo-controlled study using transcranial magnetic stimulation and 7T 1H-MRS |
| title_short | Acute gabapentin administration in healthy adults. A double-blind placebo-controlled study using transcranial magnetic stimulation and 7T 1H-MRS |
| title_sort | acute gabapentin administration in healthy adults a double blind placebo controlled study using transcranial magnetic stimulation and 7t 1h mrs |
| topic | Gamma-aminobutyric acid (GABA) Glutamate (Glu) Glutamine (Gln) Magnetic resonance spectroscopy (MRS) Transcranial magnetic stimulation (TMS) Short interval intracortical inhibition (SICI) |
| url | http://www.sciencedirect.com/science/article/pii/S2666956021000015 |
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