Effects of gabapentin on cocaine self-administration, cocaine-triggered relapse and cocaine-enhanced nucleus accumbens dopamine in rats

Peng, Xiao‐Qing; Li, Xia; Li, Jie; Ramachandran, P. Veeraraghavan; Gagare, Pravin D.; Pratihar, Debarshi; Ashby, Charles R.; Gardner, Eliot L.; Xi, Zheng‐Xiong

doi:10.1016/j.drugalcdep.2007.09.019

Cited by 26 publications

(26 citation statements)

References 55 publications

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“…failed to inhibit i.v. cocaine self-administration under FR2 reinforcement or cocaine-triggered reinstatement of cocaine-seeking behavior in rats [170]. Congruent with our findings, Filip et al .…”

Section: Gaba-based Medication Discoverysupporting

confidence: 89%

Hypothesis-Driven Medication Discovery for the Treatment of Psychostimulant Addiction

Xi¹,

Gardner²

2008

CDAR

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Psychostimulant abuse is a serious social and health problem, for which no effective treatments currently exist. A number of review articles have described predominantly ‘clinic’-based pharmacotherapies for the treatment of psychostimulant addiction, but none have yet been shown to be definitively effective for use in humans. In the present article, we review various ‘hypothesis’- or ‘mechanism’-based pharmacological agents that have been studied at the preclinical level and evaluate their potential use in the treatment of psychostimulant addiction in humans. These compounds target brain neurotransmitter or neuromodulator systems, including dopamine (DA), γ-aminobutyric acid (GABA), endocannabinoid, glutamate, opioid and serotonin, which have been shown to be critically involved in drug reward and addiction. For drugs in each category, we first briefly review the role of each neurotransmitter system in psychostimulant actions, and then discuss the mechanistic rationale for each drug’s potential anti-addiction efficacy, major findings with each drug in animal models of psychostimulant addiction, abuse liability and potential problems, and future research directions. We conclude that hypothesis-based medication development strategies could significantly promote medication discovery for the effective treatment of psychostimulant addiction.

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Section: Gaba-based Medication Discoverysupporting

confidence: 89%

Hypothesis-Driven Medication Discovery for the Treatment of Psychostimulant Addiction

Xi¹,

Gardner²

2008

CDAR

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“…Di Matteo et al (2000) showed that administration of Amt also increased dopamine release in the rat NAc, suggesting the possible involvement of serotonin 5HT 2C receptors. Peng et al (2008), in turn, failed to demonstrate any alteration of the dopamine level within the NAc using Gb or even after cocaine selfadministration, cocaine-triggered relapse and cocaineenhanced NAc dopamine in rats. Our results suggest that drugs which, according to previous studies, exhibit the capacity of increasing dopamine concentrations in the NAc, such as Amt, Me and Mo, also induced an increased GFAP immunoreactivity in this region, probably by enhancing the astrocyte activity of clearing excess dopamine.…”

Section: Discussionmentioning

confidence: 99%

Astrocytic expression of GFAP and serum levels of IL-1β and TNF-α in rats treated with different pain relievers

Amaral

Dossa

Viebig

et al. 2016

Braz. J. Pharm. Sci.

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Pro-inflammatory cytokines and glial cells, especially microglial cells, have been implicated in persistent pain sensitization. Less is known about the role of astrocytes in pain regulation. This study aimed to observe the expression of the astrocytic biomarker glial fibrillary acidic protein (GFAP) and the serum levels of interleukin 1 beta (IL-1β) and tumor necrosis factor alpha (TNF-α) after short-term administration of central pain relievers in rats not submitted to noxious stimuli. Male Wistar rats were divided into five groups, receiving for nine days-(1) amitriptyline (Amt-10 mg/kg/day, by gavage); (2) gabapentin (Gb-60 mg/kg/day, by gavage; (3) methadone (Me-4.5 mg/kg/day, intraperitoneal route [IP]); (4) morphine (Mo-10 mg/kg/day, IP); or (5) 0.9% saline solution, IP. Brain samples were collected for immunohistochemical study of GFAP expression in the mesencephalon and nucleus accumbens (NAc). The area of GFAP-positive cells was calculated using MetaMorph software and serum levels of IL-1β and TNF-α were measured by enzyme-linked immunosorbent assay. Serum TNF-α levels were decreased in the groups treated with Mo, Me and Gb, but not in the Amt-treated group. IL-1β decreased only in rats treated with Me. The astrocytic expression of GFAP was decreased in the brainstem with all drugs, while it was increased in the NAc with Amt, Me and Mo.

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“…The underlying mechanism for these behavioral effects has long been thought to be GVG-enhanced extracellular GABA with consequent inhibition of addictive drug-induced increases in extracellular dopamine (DA) in the nucleus accumbens (NAc) (Dewey et al 1997; Morgan and Dewey 1998; Schiffer et al 2000). Contrary to this view, we have recently reported that GVG or gabapentin, whether administered systemically or locally into the NAc, fails to alter either basal or cocaine-enhanced extracellular DA (Peng et al 2008a,b), suggesting that a non-DA mechanism may underlie the action of GVG or gabapentin in animal models of drug addiction (Peng et al 2008a, b; Xi and Gardner 2008). …”

Section: Introductionmentioning

confidence: 73%

Gamma-vinyl GABA increases nonvesicular release of GABA and glutamate in the nucleus accumbens in rats via action on anion channels and GABA transporters

Peng

Gardner

2009

Psychopharmacology

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Rationale γ-Amino butyric acid (GABA) is a well-characterized inhibitory neurotransmitter in the central nervous system, which may also stimulate nonvesicular release of other neurotransmitters under certain conditions. We have recently reported that γ-vinyl GABA (GVG), an irreversible GABA transaminase inhibitor, elevates extracellular GABA but fails to alter dopamine release in the nucleus accumbens (NAc). Objectives Here, we investigated the mechanism(s) by which GVG elevates extracellular GABA levels and whether GVG also alters glutamate release in the NAc. Materials and methods In vivo microdialysis was used to simultaneously measure extracellular NAc GABA and glutamate before and after GVG administration in freely moving rats. Results Systemic administration of GVG or intra-NAc local perfusion of GVG significantly increased extracellular NAc GABA and glutamate. GVG-enhanced GABA was completely blocked by intra-NAc local perfusion of 5-nitro-2, 3-(phenylpropylamino)-benzoic acid (NPPB), a selective anion channel blocker and partially blocked by SKF89976A, a type 1 GABA transporter inhibitor. GVG-enhanced glutamate was completely blocked by NPPB or SKF89976A. Tetrodotoxin, a voltage-dependent Na+-channel blocker, failed to alter GVG-enhanced GABA and glutamate. Conclusions These data suggest that GVG-enhanced extracellular GABA and glutamate are mediated predominantly by the opening of anion channels and partially by the reversal of GABA transporters. Enhanced extracellular glutamate may functionally attenuate the pharmacological action of GABA and prevent enhanced GABA-induced excess inhibition.

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Effects of gabapentin on cocaine self-administration, cocaine-triggered relapse and cocaine-enhanced nucleus accumbens dopamine in rats

Cited by 26 publications

References 55 publications

Hypothesis-Driven Medication Discovery for the Treatment of Psychostimulant Addiction

Hypothesis-Driven Medication Discovery for the Treatment of Psychostimulant Addiction

Astrocytic expression of GFAP and serum levels of IL-1β and TNF-α in rats treated with different pain relievers

Gamma-vinyl GABA increases nonvesicular release of GABA and glutamate in the nucleus accumbens in rats via action on anion channels and GABA transporters

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