Gabapentin Increases a Tonic Inhibitory Conductance in Hippocampal Pyramidal Neurons

Cheng, Victor; Bonin, Robert P.; Chiu, Mary; Newell, J. Glen; MacDonald, John F.; Orser, Beverley A.

doi:10.1097/00000542-200608000-00015

Cited by 22 publications

(18 citation statements)

References 43 publications

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“…A cyclohexane ring was added to the carbon backbone of GABA to facilitate the transfer of the drug across the blood-brain barrier. 43 Surprisingly, gabapentin does not bind to or directly modulate GABA A receptors, [44][45][46] and it does not modulate GABA B receptors, except at high concentrations. 47 On the other hand, in healthy volunteers and studies involving patients with epilepsy, GABA levels were increased after oral ingestion of gabapentin.…”

Section: Discussionmentioning

confidence: 99%

Gabapentin reduces preoperative anxiety and pain catastrophizing in highly anxious patients prior to major surgery: a blinded randomized placebo-controlled trial

Clarke

Kirkham

Orser

et al. 2013

Can J Anesth/J Can Anesth

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Section: Discussionmentioning

confidence: 99%

Gabapentin reduces preoperative anxiety and pain catastrophizing in highly anxious patients prior to major surgery: a blinded randomized placebo-controlled trial

Clarke

Kirkham

Orser

et al. 2013

Can J Anesth/J Can Anesth

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“…The doses (10 -75 M) of gabapentin used in the present study are similar to those tested in other cellular studies such as in rat entorhinal slices (10 -100 M) (Cunningham et al, 2004;Brown and Randall, 2005) and rat trigeminal nucleus (30 M) (Maneuf et al, 2001). In contrast, low concentrations of gabapentin (Ͻ5 M) are effective in DRG (Yang et al, 2005) and high doses are required in cultured neurons (1000 M) (Cheng et al, 2006). We previously found increased GABA "tone" in CeA after chronic ethanol exposure (Roberto et al, 2004a) and lack of tolerance for the acute ethanol effect (Roberto et al, 2004a).…”

Section: Discussionmentioning

confidence: 99%

Cellular and Behavioral Interactions of Gabapentin with Alcohol Dependence

Roberto¹,

Gilpin²,

O’Dell³

et al. 2008

J. Neurosci.

118

128

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Gabapentin is a structural analog of GABA that has anticonvulsant properties. Despite the therapeutic efficacy of gabapentin, its molecular and cellular mechanisms of action are unclear. The GABAergic system in the central nucleus of the amygdala (CeA) plays an important role in regulating voluntary ethanol intake. Here, we investigated the effect of gabapentin on GABAergic transmission in CeA slices, on ethanol intake, and on an anxiety measure using animal models of ethanol dependence. Gabapentin increased the amplitudes of evoked GABA receptor-mediated IPSCs (GABA-IPSCs) in CeA neurons from nondependent rats, but decreased their amplitudes in CeA of ethanol-dependent rats. Gabapentin effects were blocked in the presence of a specific GABA B receptor antagonist. The sensitivity of the GABA-IPSCs to a GABA B receptor antagonist and an agonist was decreased after chronic ethanol, suggesting that ethanol-induced neuroadaptations of GABA B receptors associated with ethanol dependence may account for the differential effects of gabapentin after chronic ethanol. Systemic gabapentin reduced ethanol intake in dependent, but not in nondependent, rats and reversed the anxiogeniclike effects of ethanol abstinence using an acute dependence model. Gabapentin infused directly into the CeA also blocked dependenceinduced elevation in operant ethanol responding. Collectively, these findings show that gabapentin reverses behavioral measures of ethanol dependence and, in turn, dependence reverses the effects of gabapentin on CeA neurons, and suggest that gabapentin represents a potential medication for treatment of alcoholism.

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“…The postulated main binding site of GBP is the alpha-2-delta subunit of voltage-dependent calcium channels (6). Recent studies also demonstrate a link to central inhibitory gabaergic pathways in the central nervous system (44,45), and research continues in an effort to elucidate the cellular mechanisms mediating the actions of the gabapentinoids. Given the likelihood of a central depressant mechanism of GBP, the interaction of GBP and central inhibitory anesthetic agents may be cumulative in the immediate postoperative period; thus, health care providers often must adjust the dose of intraoperative opioids to avoid excessive sedation when using GBP perioperatively.…”

Section: Discussionmentioning

confidence: 99%

Gabapentin decreases morphine consumption and improves functional recovery following total knee arthroplasty

Clarke¹,

Pereira²,

Kennedy³

et al. 2009

Acute Pain

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Gabapentin Increases a Tonic Inhibitory Conductance in Hippocampal Pyramidal Neurons

Abstract: Gabapentin increases a tonic inhibitory conductance in mammalian neurons. High-affinity GABAA receptors that generate the tonic conductance may detect small increases in the ambient concentration of neurotransmitter caused by gabapentin.

Cited by 22 publications

References 43 publications

Gabapentin reduces preoperative anxiety and pain catastrophizing in highly anxious patients prior to major surgery: a blinded randomized placebo-controlled trial

Gabapentin reduces preoperative anxiety and pain catastrophizing in highly anxious patients prior to major surgery: a blinded randomized placebo-controlled trial

Cellular and Behavioral Interactions of Gabapentin with Alcohol Dependence

Gabapentin decreases morphine consumption and improves functional recovery following total knee arthroplasty

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