Brain GABA and Glutamate Concentrations Following Chronic Gabapentin Administration: A Convenience Sample Studied During Early Abstinence From Alcohol.

Dieter J Meyerhoff,Timothy C Durazzo,David L Pennington,Donna E Murray

doi:10.3389/fpsyt.2018.00078

Abstract

Gabapentin (GBP), a GABA analog that may also affect glutamate (Glu) production, can normalize GABA and Glu tone during early abstinence from alcohol, effectively treating withdrawal symptoms and facilitating recovery. Using in vivo magnetic resonance spectroscopy, we tested the degree to which daily GBP alters regional brain GABA and Glu levels in short-term abstinent alcohol-dependent individuals. Regional metabolite levels were compared between 13 recently abstinent alcohol-dependent individuals who had received daily GBP for at least 1 week (GBP+) and 25 matched alcohol-dependent individuals who had not received GBP (GBP−). Magnetic resonance spectra from up to five different brain regions were analyzed to yield absolute GABA and Glu concentrations. GABA and Glu concentrations in the parieto-occipital cortex were not different between GBP− and GBP+. Glu levels in anterior cingulate cortex, dorsolateral prefrontal cortex, and basal ganglia did not differ between GBP− and GBP+. However, in a subgroup of individuals matched on age, sex, and abstinence duration, GBP+ had markedly lower Glu in the frontal white matter (WM) than GBP−, comparable to concentrations found in light/non-drinking controls. Furthermore, lower frontal WM Glu in GBP+ correlated with a higher daily GBP dose. Daily GBP treatment at an average of 1,600 mg/day for at least 1 week was not associated with altered cortical GABA and Glu concentrations during short-term abstinence from alcohol, but with lower Glu in frontal WM. GBP for the treatment of alcohol dependence may work through reducing Glu in WM rather than increasing cortical GABA.

Highlights

Administered gabapentin (GBP), a GABA analog and anticonvulsant that is absorbed and crosses the blood–brain barrier, has shown promise in treating seizures and neuropathic pain
Glu levels in POC and in our frontal cortical (ACC, DLPFC) and basal ganglia VOIs did not differ between the groups
GBP treatment at a median dose of 1,200 mg/day for at least 1 week was not associated with altered cortical GABA or cortical and basal ganglia Glu levels in short-term abstinent alcoholdependent individuals in outpatient treatment (ALC)

Summary

Introduction

Administered gabapentin (GBP), a GABA analog and anticonvulsant that is absorbed and crosses the blood–brain barrier, has shown promise in treating seizures and neuropathic pain. Single doses of 150 or 300 mg of GBP did not change MRS-detectable GABA or Glu levels in the prefrontal or occipital cortices of healthy controls [9]. 1H MRS demonstrated dose-dependent increases of initially low occipital cortical GABA levels after an initial dose and—to a lesser degree—after daily treatment with GBP [10,11,12]. As with acute GBP administration to healthy controls [8], epilepsy patients with the greatest GABA increases had the lowest pretreatment GABA levels. The epilepsy patients who demonstrated the best seizure control with GBP administration had above normal brain GABA concentrations.

Methods

Results

Conclusion