Activation of the cannabinoid receptor by Δ9-tetrahydrocannabinol reduces γ-aminobutyric acid uptake in the globus pallidus

Maneuf, Yannick P.; Nash, Joanne E.; Crossman, Alan R.; Brotchie, Jonathan M.

doi:10.1016/0014-2999(96)00326-3

Cited by 128 publications

(64 citation statements)

References 17 publications

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“…In line with our results, Giuffrida et al (1999) have shown reciprocal interactions between endocannabinoid and dopaminergic systems in normal conditions where CB1 blockade facilitates dopaminergic effects. Some authors (e.g., Sieradzan et al, 2001) have proposed that the effects of cannabinoid antagonists are mediated by increase of GABA reuptake in GPe through presynaptic CB1 receptors (Maneuf et al, 1996). However, the facts that CB1 receptor activation also reduces GABA release and has important actions in striatum and other regions (Herkenham et al, 1990) rather suggest the interaction of various mechanisms to produce the observed behavioral effects following systemic administration of CB1 antagonists.…”

Section: Discussionmentioning

confidence: 99%

“…In the internal globus pallidus segment/ substantia nigra pars reticulata, the net effects of CB1 stimulation are uncertain because of combined inhibitory interaction with GABA release and uptake from striatal terminals as well as glutamate release from the subthalamic nucleus (Szabo et al, 2000;Wallmichrath and Szabo, 2002). However, in GPe, the main effects are thought to be mediated by inhibition of GABA reuptake that results in increased GABA transmission and inhibition of the subthalamic nucleus (Maneuf et al, 1996). Through this mechanism in the indirect striatal output pathway, CB1 antagonists may synergize the L-DOPA antiparkinsonian effects.…”

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confidence: 99%

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Blockade of Cannabinoid Type 1 Receptors Augments the Antiparkinsonian Action of Levodopa without Affecting Dyskinesias in 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine-Treated Rhesus Monkeys

Cao

Liang²,

Hadcock³

et al. 2007

J Pharmacol Exp Ther

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Drugs acting at cannabinoid type 1 receptors (CB1) have modulatory effects on glutamate and GABA neurotransmission in basal ganglia; thus, they potentially affect motor behavior in the parkinsonian setting. Preclinical trials with diverse cannabinoid agents have shown varied results, and the precise effects of blocking cannabinoid CB1 receptors remain uncertain. We tested behavioral effects of the selective antagonist 1-[7-(2-chlorophenyl)-8-(4-chlorophenyl)-2-methylpyrazolo[1,5-a]-[1,3,5]triazin-4-yl]-3-ethylaminoazetidine-3-carboxylic acid amide benzenesulfonate (CE) as monotherapy and in combination with L-DOPA in treatment-naive and L-DOPA-primed 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated rhesus monkeys with moderate and severe parkinsonism. Motor disability and L-DOPA-induced dyskinesias were scored with a standardized scale after subcutaneous drug administration, and plasma levels of L-DOPA were determined by highperformance liquid chromatography/electrochemical detection. CE doses ranged from 0.03 to 1 mg/kg, and L-DOPA methyl ester doses were selected as optimal and suboptimal doses (maximal and 50% of maximal responses, respectively). CE had no intrinsic effects on motor behavior regardless of the degree of parkinsonism (moderate or severe groups) or previous drug exposure ("de novo" or after L-DOPA priming). Initial CE administration did not affect development of L-DOPA antiparkinsonian responses. In coadministration trials, CE, in a dose-dependent manner, increased responses to L-DOPA (suboptimal doses). These effects were seen in both moderate and severely parkinsonian monkeys as a 30% increase of, predominantly, response duration with no effects on L-DOPA pharmacokinetics. CE did not modify levodopa-induced dyskinesias. These results suggest that selective cannabinoid CB1 antagonists may enhance the antiparkinsonian action of dopaminomimetics and possibly facilitate the use of lower doses, thereby reducing side effects.Parkinson's disease (PD) is characterized principally by progressive neurodegeneration of the nigrostriatal dopamine system and its accompanying motor dysfunction: tremor, rigidity, and bradykinesia. Dopamine replacement with the dopamine precursor L-DOPA improves motor symptoms, although long-term therapy causes disabling side effects, such as varied motor complications (response fluctuations and dyskinesias) (Nutt, 2000;Obeso et al., 2000). Because of these shortcomings, therapies that act as either adjuncts or alternatives to L-DOPA by modulating its effects and reducing adverse reactions may help in restoring normal function in the late-stage disease. Putative bases for developing new therapies lie in the interaction of dopamine with other neurotransmitter systems in basal ganglia. In fact, pathogenic mechanisms of L-DOPA-induced motor complications involve the glutamate system as the major transmitter driving the activity of striatal neurons (Chase and Oh, 2000). Other

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Blockade of Cannabinoid Type 1 Receptors Augments the Antiparkinsonian Action of Levodopa without Affecting Dyskinesias in 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine-Treated Rhesus Monkeys

Cao

Liang²,

Hadcock³

et al. 2007

J Pharmacol Exp Ther

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“…The mechanisms whereby CB 1 agonists might alleviate dyskinesia remain hypothetical but include a reduction of corticostriatal glutamatergic transmission and a reduction of GABA reuptake in the GPi (Maneuf et al, 1996;Sieradzan et al, 2001;Fox et al, 2002b), although not all endogenous cannabinoids appear to mediate this latter effect (Venderova et al, 2005). However, these proposed antidyskinetic mechanisms for CB 1 agonists are difficult to reconcile with the antidyskinetic efficacy of the CB 1 antagonist rimonabant.…”

Section: A Cannabinoid Receptorsmentioning

confidence: 99%

The Pharmacology of l-DOPA-Induced Dyskinesia in Parkinson’s Disease

Huot

Johnston²,

Koprich³

et al. 2013

Pharmacol Rev

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288

230

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“…On the other hand it has been demonstrated that cannabinoids enhance GABAergic transmission in the GPl (Maneuf et al 1996) and, therefore, enhance inhibitory motor effects resulting in reduced voluntary movements and Parkinson-like symptoms (Wickens and Pertwee 1995). Cannabinoid receptors are located at high concentrations on GABAergic terminals projecting from the striatum to the globus pallidus (GP) and substantia nigra pars reticulata (SNr) (Herkenham et al 1990).…”

Section: Discussionmentioning

confidence: 99%

Combined Treatment of Tourette Syndrome with Δ⁹-THC and Dopamine Receptor Antagonists

Müller‐Vahl

Schneider

Emrich

2002

Journal of Cannabis Therapeutics

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SUMMARY.Animal studies suggest that cannabinoid receptor agonists might enhance the effect of dopamine receptor antagonists (neuroleptics, NL) in hyperkinetic movement disorders. In Tourette syndrome, NL are the most effective drugs for the treatment of tics. Recent clinical trials demonstrated that delta-9-tetrahydrocannabinol (∆ 9 -THC) also produces a tic-suppressing effect. In this single case study in a 24 years old female suffering from TS with extreme tics, it is suggested for the first time that ∆ 9 -THC may be useful in augmenting the pharmacological response to atypical NL such as amisulpride and risperidone in TS patients. No serious adverse reactions occurred. Controlled studies are necessary to confirm this initial report.

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Activation of the cannabinoid receptor by Δ9-tetrahydrocannabinol reduces γ-aminobutyric acid uptake in the globus pallidus

Cited by 128 publications

References 17 publications

Blockade of Cannabinoid Type 1 Receptors Augments the Antiparkinsonian Action of Levodopa without Affecting Dyskinesias in 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine-Treated Rhesus Monkeys

Blockade of Cannabinoid Type 1 Receptors Augments the Antiparkinsonian Action of Levodopa without Affecting Dyskinesias in 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine-Treated Rhesus Monkeys

The Pharmacology of l-DOPA-Induced Dyskinesia in Parkinson’s Disease

Combined Treatment of Tourette Syndrome with Δ⁹-THC and Dopamine Receptor Antagonists

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Activation of the cannabinoid receptor by Δ9-tetrahydrocannabinol reduces γ-aminobutyric acid uptake in the globus pallidus

Cited by 128 publications

References 17 publications

Blockade of Cannabinoid Type 1 Receptors Augments the Antiparkinsonian Action of Levodopa without Affecting Dyskinesias in 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine-Treated Rhesus Monkeys

Blockade of Cannabinoid Type 1 Receptors Augments the Antiparkinsonian Action of Levodopa without Affecting Dyskinesias in 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine-Treated Rhesus Monkeys

The Pharmacology of l-DOPA-Induced Dyskinesia in Parkinson’s Disease

Combined Treatment of Tourette Syndrome with Δ9-THC and Dopamine Receptor Antagonists

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Product

Resources

About

Combined Treatment of Tourette Syndrome with Δ⁹-THC and Dopamine Receptor Antagonists