Cannabinoid CB<sub>1</sub>Receptor Antagonist AM251 Inhibits Cocaine-Primed Relapse in Rats: Role of Glutamate in the Nucleus Accumbens

Xi, Zheng‐Xiong; Gilbert, Jeremy; Peng, Xiao‐Qing; Pak, Arlene C.; Li, Xia; Gardner, Eliot L.

doi:10.1523/jneurosci.0726-06.2006

Cited by 154 publications

(204 citation statements)

References 35 publications

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“…Intravenous cocaine self-administration and reinstatement of drug-seeking behavior are commonly used animal models to predict rewarding effects and relapse-provoking potential of addictive drugs in humans (Shaham et al, 2003;Xi et al, 2005Xi et al, , 2006. Congruent with the present findings, Filip et al (2007) recently reported that lower doses of gabapentin (10-30 mg/kg, 1 h prior to testing) failed to alter cocaine self-administration and cocaine-induced relapse in rats (Filip et al, 2007).…”

Section: Discussionsupporting

confidence: 68%

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

Peng

et al. 2008

Drug and Alcohol Dependence

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Gabapentin is a γ-aminobutyric acid (GABA) analogue, with GABAmimetic pharmacological properties. Gabapentin is used for the treatment of seizures, anxiety and neuropathic pain. It has been proposed that gabapentin may be useful in the treatment of cocaine dependence. However, clinical trials with gabapentin have shown conflicting results, while preclinical studies are sparse. In the present study, we investigated the effects of gabapentin on intravenous cocaine self-administration and cocaine-triggered reinstatement of drug-seeking behavior, as well as on cocaine-enhanced dopamine (DA) in the nucleus accumbens (NAc). We found that gabapentin (25-200 mg/kg, i.p., 30 min or 2 h prior to cocaine) failed to inhibit intravenous cocaine (0.5 mg/kg/infusion) selfadministration under a fixed-ratio reinforcement schedule or cocaine-triggered reinstatement of cocaine-seeking behavior. In vivo microdialysis showed that the same doses of gabapentin produced a modest increase (∼50%, p < 0.05) in extracellular NAc GABA levels, but failed to alter either basal or cocaine-enhanced NAc DA. These data suggest that gabapentin is a weak GABA-mimic drug. At the doses tested, it has no effect in the addiction-related animal behavioral models here tested. This

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Section: Discussionsupporting

confidence: 68%

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

Peng

et al. 2008

Drug and Alcohol Dependence

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“…At earlier time points AM251 blocked URB597-mediated effects; however, this block via CB1 receptors was not sustained throughout the duration of recording. Other studies have demonstrated prolonged effects (>2 h) at CB1 receptors by AM251 in vivo (Gardiner et al, 2002;Xi et al, 2006), suggesting the observations are not explained by a pharmacokinetic effect. SR141716A also blocked the effects of URB597 on firing rate.…”

Section: Discussionmentioning

confidence: 70%

Inhibition of endocannabinoid metabolism attenuates enhanced hippocampal neuronal activity induced by kainic acid

Coomber

O’Donoghue

Mason

2008

Synapse

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The endogenous cannabinoid system regulates neuronal excitability. The effects of inhibiting fatty acid amide hydrolase (FAAH), the enzyme responsible for metabolism of the endocannabinoid anandamide, on kainic acid (KA)-induced neuronal activity were investigated in the rat in vivo, using the selective FAAH inhibitor URB597. Hippocampal neuronal ensemble unit activity was recorded in isoflurane-anesthetized rats using 16-wire microelectrode arrays. Separate groups of rats were administered with single doses of KA alone, KA and URB597 (0.3 or 1 mg kg 21 , i.p.), or URB597 (1 mg kg 21 ) alone. The role of the cannabinoid CB1 receptor in mediating the effects of URB597 was explored using the CB1 selective antagonists AM251, either alone or prior to KA and URB597 (1 mg kg 21 ) administration, and SR141716A, administered prior to KA and URB597 (1 mg kg 21 ). Neuronal firing and burst firing rates were examined in animals with confirmed dorsal hippocampal placements. KA induced an increase in both firing and burst firing rates, effects which were attenuated by URB597 in a dose-related manner. Pretreatment with AM251 or SR141716A partly attenuated the URB597-mediated effects on firing and burst firing rate. Rats treated with AM251 or URB597 alone did not exhibit any significant change in either firing or burst firing rates compared with basal activity. These results suggest that the inhibition of endocannabinoid metabolism can suppress hyperexcitability in the rat hippocampus, partly via a CB1 receptormediated mechanism. Synapse 62: 746-755, 2008. V

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“…Microdialysis protocols and probe construction were as reported previously (Xi et al, 2006). Guide cannulae (20G, Plastics One, Roanoke, VA) were surgically implanted into the NAc (AP+1.6 mm, ML±1.8 mm, DV-4.3 mm, angled 6° from vertical) using standard surgical and stereotaxic techniques.…”

Section: In Vivo Microdialysismentioning

confidence: 99%

“…Microdialysate DA was measured by high performance liquid chromatography (HPLC) with an ESA (ESA Biosciences, Chelmsford, MA) electrochemical (EC) detection system as described previously (Xi et al, 2006), upgraded by a Coulochem III EC detector. Areas under the curve (AUC) for DA were measured and quantified with external standard curves.…”

Section: In Vivo Microdialysismentioning

confidence: 99%

Levo-tetrahydropalmatine inhibits cocaine's rewarding effects: Experiments with self-administration and brain-stimulation reward in rats

Zheng

et al. 2007

Neuropharmacology

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It was recently reported that levo-tetrahydropalmatine (l-THP), a dopamine (DA) D 1 and D 2 receptor antagonist purified from the Chinese herb Stephanie, appears to be effective in attenuating cocaine self-administration, cocaine-triggered reinstatement and cocaine-induced conditioned place preference in preclinical animal models. The present study was designed to contrast l-THP's effects on cocaine self-administration under fixed-ratio (FR) and progressive-ratio (PR) reinforcement, and to study l-THP's effects on cocaine-enhanced brain stimulation reward (BSR). Systemic administration of l-THP produced dose-dependent, biphasic effects, i.e., low-to-moderate doses (1, 3, 10 mg/kg) increased, while a high dose (20 mg/kg) inhibited cocaine self-administration behavior under FR2 reinforcement. The increased cocaine self-administration is likely a compensatory response to a reduction in cocaine's rewarding effects, because the same low doses of l-THP dosedependently attenuated cocaine self-administration under PR reinforcement and also attenuated cocaine-enhanced BSR. These attenuations of PR cocaine self-administration and cocaine-enhanced BSR are unlikely due to l-THP-induced sedation or locomotor inhibition, because only 10 mg/kg, but not 1-3 mg/kg of l-THP inhibited locomotion, sucrose self-administration and asymptotic operant performance in the BSR paradigm. In vivo microdialysis demonstrated that l-THP slightly elevates extracellular nucleus accumbens DA by itself, but dose-dependently potentiates cocaine-augmented DA, suggesting that a postsynaptic, rather than presynaptic, DA receptor antagonism underlies l-THP's actions on cocaine reward. Together, the present data, combined with previous findings, support the potential use of l-THP for treatment of cocaine addiction.

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Cannabinoid CB₁Receptor Antagonist AM251 Inhibits Cocaine-Primed Relapse in Rats: Role of Glutamate in the Nucleus Accumbens

Cited by 154 publications

References 35 publications

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

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

Inhibition of endocannabinoid metabolism attenuates enhanced hippocampal neuronal activity induced by kainic acid

Levo-tetrahydropalmatine inhibits cocaine's rewarding effects: Experiments with self-administration and brain-stimulation reward in rats

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Cannabinoid CB1Receptor Antagonist AM251 Inhibits Cocaine-Primed Relapse in Rats: Role of Glutamate in the Nucleus Accumbens

Cited by 154 publications

References 35 publications

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

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

Inhibition of endocannabinoid metabolism attenuates enhanced hippocampal neuronal activity induced by kainic acid

Levo-tetrahydropalmatine inhibits cocaine's rewarding effects: Experiments with self-administration and brain-stimulation reward in rats

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Cannabinoid CB₁Receptor Antagonist AM251 Inhibits Cocaine-Primed Relapse in Rats: Role of Glutamate in the Nucleus Accumbens