Acute effects of gabapentin and pregabalin on rat forebrain cellular GABA, glutamate, and glutamine concentrations

被引：85

作者：

Errante, LD ^{[1
]}

Petroff, OAC ^{[1
]}

机构：

[1] Yale Univ, Sch Med, Dept Neurol, New Haven, CT 06520 USA

来源：

SEIZURE-EUROPEAN JOURNAL OF EPILEPSY | 2003年 / 12卷 / 05期

关键词：

gabapentin; pregabalin; glutamate; GABA; MRS; brain;

D O I：

10.1016/S1059-1311(02)00295-9

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

The effects of antiepileptic drugs, gabapentin, pregabalin and vigabatrin, on brain gamma-aminobutyric acid (GABA), glutamate and glutamine concentrations were studied in Long Evans rats using proton magnetic resonance spectroscopy (MRS) of perchloric acid extracts. Cellular glutamate concentrations significantly decreased by 7% (P < 0.05) 2 hours after intraperitoneal injection of 100 mg/kg gabapentin and 4% (P < 0.05) with 1000 mg/kg. No differences were observed in cellular GABA and cellular glutamine concentrations in rats treated with gabapentin. Pregabalin, an analogue of gadapentin, significantly decreased cellular glutamate concentrations by 4% (P < 0.05), while no effect was observed on cellular GABA or glutamine concentrations in the healthy rat forebrain. Vigabatrin, used as a positive control to increase GABA levels, produced a 50% increase in cellular GABA compared to saline treated rats (P < 0.003). Although, gabapentin and pregabalin are anticonvulsants designed to mimic GABA, these drugs do not raise cellular GABA levels acutely but modestly decreased cellular glutamate levels in our healthy rat forebrain model. (C) 2003 BEA Trading Ltd. Published by Elsevier Science Ltd. All rights reserved.

引用

页码：300 / 306

页数：7

共 59 条

[1] Transfer of glutamine between astrocytes and neurons [J].

Bröer, S ;

Brookes, N .

JOURNAL OF NEUROCHEMISTRY, 2001, 77 (03) :705-719

[2]

Bryans JS, 1999, MED RES REV, V19, P149, DOI 10.1002/(SICI)1098-1128(199903)19:2<149::AID-MED3>3.0.CO

[3]

2-B

[4] Activation of two types of brain glutamate dehydrogenase isoproteins by gabapentin [J].

Cho, SW ;

Cho, EH ;

Choi, SY .

FEBS LETTERS, 1998, 426 (02) :196-200

[5] GLUTAMATE IMMUNOREACTIVITY IN RAT CEREBRAL-CORTEX IS REVERSIBLY ABOLISHED BY 6-DIAZO-5-OXO-L-NORLEUCINE (DON), AN INHIBITOR OF PHOSPHATE-ACTIVATED GLUTAMINASE [J].

CONTI, F ;

MINELLI, A .

JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY, 1994, 42 (06) :717-726

[6] Glutamate uptake [J].

Danbolt, NC .

PROGRESS IN NEUROBIOLOGY, 2001, 65 (01) :1-105

[7] NEOCORTICAL NEURONAL DIVERSITY - CHEMICAL HETEROGENEITY REVEALED BY COLOCALIZATION STUDIES OF CLASSIC NEUROTRANSMITTERS, NEUROPEPTIDES, CALCIUM-BINDING PROTEINS, AND CELL-SURFACE MOLECULES [J].

DEFELIPE, J .

CEREBRAL CORTEX, 1993, 3 (04) :273-289

[8] Inhibition of K+-evoked glutamate release from rat neocortical and hippocampal slices by gabapentin [J].

Dooley, DJ ;

Mieske, CA ;

Borosky, SA .

NEUROSCIENCE LETTERS, 2000, 280 (02) :107-110

[9] Metabolic approach of absence seizures in a genetic model of absence epilepsy, the GAERS: Study of the leucine-glutamate cycle [J].

Dufour, F ;

Nalecz, KA ;

Nalecz, MJ ;

Nehlig, A .

JOURNAL OF NEUROSCIENCE RESEARCH, 2001, 66 (05) :923-930

[10] Effects of anti-epileptic drugs on glutamine synthetase activity in mouse brain [J].

Fraser, CM ;

Sills, GJ ;

Forrest, G ;

Thompson, GG ;

Brodie, MJ .

BRITISH JOURNAL OF PHARMACOLOGY, 1999, 126 (07) :1634-1638

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