Cocaine depresses GABA(A) current of hippocampal neurons

Jiang Hong Ye; Philip L. Liu; Wen Hsien Wu; Joseph J. McArdle

doi:10.1016/S0006-8993(97)00782-8

Cocaine depresses GABA(A) current of hippocampal neurons

Jiang Hong Ye, Philip L. Liu, Wen Hsien Wu, Joseph J. McArdle

Research output: Contribution to journal › Article › peer-review

41 Scopus citations

Abstract

Although blockade of dopamine re-uptake and the resulting elevation of excitatory agonists is commonly thought the primary mechanism of cocaine- induced seizures, it is possible that other neurotransmitters such as γ- aminobutyric acid (GABA) are involved. To examine this possibility, the effects of cocaine on the whole cell GABA current (1(GABA)) of freshly isolated rat hippocampal neurons were investigated with the patch-clamp technique. Preincubation or acute application of cocaine reversibly suppressed I(GABA). The IC₅₀ was 127 μM when cocaine was applied before the application of GABA. The concentration-response relations of cocaine in various GABA concentrations revealed that cocaine inhibited I(GABA) non- competitively. This effect of cocaine appeared to be independent of voltage. The present study suggests that the GABA receptor/channel complex is also a target for cocaine's action. The suppression of I(GABA) may contribute to cocaine-induced seizures.

Original language	English (US)
Pages (from-to)	169-175
Number of pages	7
Journal	Brain research
Volume	770
Issue number	1-2
DOIs	https://doi.org/10.1016/S0006-8993(97)00782-8
State	Published - Oct 3 1997
Externally published	Yes

All Science Journal Classification (ASJC) codes

Neuroscience(all)
Molecular Biology
Clinical Neurology
Developmental Biology

Keywords

Cocaine
Hippocampal neuron
Local anesthetic toxicity
Patch clamp
Seizure
Whole cell GABA(A) current
γ-Aminobutyric acid receptor/channel

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10.1016/S0006-8993(97)00782-8

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title = "Cocaine depresses GABA(A) current of hippocampal neurons",

abstract = "Although blockade of dopamine re-uptake and the resulting elevation of excitatory agonists is commonly thought the primary mechanism of cocaine- induced seizures, it is possible that other neurotransmitters such as γ- aminobutyric acid (GABA) are involved. To examine this possibility, the effects of cocaine on the whole cell GABA current (1(GABA)) of freshly isolated rat hippocampal neurons were investigated with the patch-clamp technique. Preincubation or acute application of cocaine reversibly suppressed I(GABA). The IC50 was 127 μM when cocaine was applied before the application of GABA. The concentration-response relations of cocaine in various GABA concentrations revealed that cocaine inhibited I(GABA) non- competitively. This effect of cocaine appeared to be independent of voltage. The present study suggests that the GABA receptor/channel complex is also a target for cocaine's action. The suppression of I(GABA) may contribute to cocaine-induced seizures.",

keywords = "Cocaine, Hippocampal neuron, Local anesthetic toxicity, Patch clamp, Seizure, Whole cell GABA(A) current, γ-Aminobutyric acid receptor/channel",

author = "Ye, {Jiang Hong} and Liu, {Philip L.} and Wu, {Wen Hsien} and McArdle, {Joseph J.}",

note = "Funding Information: This work was supported by a research grant from UMD, New Jersey Medical School to J.H.Y. The authors thank Drs. K. Krnjevi{\v c}, J.P. Dilger and L. Liu for their helpful comments on this work.",

year = "1997",

month = oct,

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doi = "10.1016/S0006-8993(97)00782-8",

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AU - Ye, Jiang Hong

AU - Liu, Philip L.

AU - Wu, Wen Hsien

AU - McArdle, Joseph J.

N1 - Funding Information: This work was supported by a research grant from UMD, New Jersey Medical School to J.H.Y. The authors thank Drs. K. Krnjevič, J.P. Dilger and L. Liu for their helpful comments on this work.

PY - 1997/10/3

Y1 - 1997/10/3

N2 - Although blockade of dopamine re-uptake and the resulting elevation of excitatory agonists is commonly thought the primary mechanism of cocaine- induced seizures, it is possible that other neurotransmitters such as γ- aminobutyric acid (GABA) are involved. To examine this possibility, the effects of cocaine on the whole cell GABA current (1(GABA)) of freshly isolated rat hippocampal neurons were investigated with the patch-clamp technique. Preincubation or acute application of cocaine reversibly suppressed I(GABA). The IC50 was 127 μM when cocaine was applied before the application of GABA. The concentration-response relations of cocaine in various GABA concentrations revealed that cocaine inhibited I(GABA) non- competitively. This effect of cocaine appeared to be independent of voltage. The present study suggests that the GABA receptor/channel complex is also a target for cocaine's action. The suppression of I(GABA) may contribute to cocaine-induced seizures.

AB - Although blockade of dopamine re-uptake and the resulting elevation of excitatory agonists is commonly thought the primary mechanism of cocaine- induced seizures, it is possible that other neurotransmitters such as γ- aminobutyric acid (GABA) are involved. To examine this possibility, the effects of cocaine on the whole cell GABA current (1(GABA)) of freshly isolated rat hippocampal neurons were investigated with the patch-clamp technique. Preincubation or acute application of cocaine reversibly suppressed I(GABA). The IC50 was 127 μM when cocaine was applied before the application of GABA. The concentration-response relations of cocaine in various GABA concentrations revealed that cocaine inhibited I(GABA) non- competitively. This effect of cocaine appeared to be independent of voltage. The present study suggests that the GABA receptor/channel complex is also a target for cocaine's action. The suppression of I(GABA) may contribute to cocaine-induced seizures.

KW - Cocaine

KW - Hippocampal neuron

KW - Local anesthetic toxicity

KW - Patch clamp

KW - Seizure

KW - Whole cell GABA(A) current

KW - γ-Aminobutyric acid receptor/channel

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Cocaine depresses GABA(A) current of hippocampal neurons

Abstract

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