Co-administration of cannabidiol and capsazepine reduces L-DOPA-induced dyskinesia in mice: Possible mechanism of action

Pereira, Maurício dos Santos; da-Silva, C.A.; Guimarães, Francisco Silveira; Del‐Bel, Elaine

doi:10.1016/j.nbd.2016.06.013

Cited by 75 publications

(68 citation statements)

References 137 publications

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“…All drugs were dissolved in 5% DMSO, 15% Tween 80 in sterile physiological saline and injected intraperitoneally at 10 ml/kg. The doses of drugs used were based on previous studies: AM404 at 10 mg/kg (Gamaleddin et al., ), MRS1477 at 10 mg/kg (Kaszas et al., ), AM251 at 1 mg/kg (Chen, Huang, Shen, MacNeil, & Fong, ), capsazepine at 5 mg/kg (dos‐Santos‐Pereira, Da‐Silva, Guimarães, & Del‐Bel, ), CP‐55,940 at 30 μg/kg (Vinod et al., ), and JZL184 at two doses: 2 and 18 mg/kg (Hartley et al., ; Oleson et al., ).…”

Section: Methodsmentioning

confidence: 99%

Bi‐directional modulation of food habit expression by the endocannabinoid system

Gianessi

Groman

Taylor

2019

Eur J of Neuroscience

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The compulsive, habitual behaviors that have been observed in individuals diagnosed with substance use disorders may be due to disruptions in the neural circuits that mediate goal‐directed actions. The endocannabinoid system has been shown to play a critical role in habit learning, but the role of this neuromodulatory system in habit expression is unclear. Here, we investigated the role of the endocannabinoid system in established habitual actions using contingency degradation in male C57BL/6 mice. We found that administration of the endocannabinoid transport inhibitor AM404 reduced habitual responding for food and that antagonism of cannabinoid receptor type 1 (CB1), but not transient receptor potential cation subfamily V (TRPV1), receptors produced a similar reduction in habitual responding. Moreover, pharmacological stimulation of CB1 receptors increased habitual responding for food. Co‐administration of an enzyme inhibitor that selectively increases the endocannabinoid 2‐arachidonoyl glycerol (2‐AG) with AM404 partially restored habitual responding for food. Together, these findings demonstrate an important role for the endocannabinoid system in the expression of habits and provide novel insights into potential pharmacological strategies for reducing habitual behaviors in mental disorders.

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Section: Methodsmentioning

confidence: 99%

Bi‐directional modulation of food habit expression by the endocannabinoid system

Gianessi

Groman

Taylor

2019

Eur J of Neuroscience

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“…2‐AG is the most abundant endogenous agonist of cannabinoid receptors (CB1/2), which are expressed in astrocytes and other cells. Drugs related to the endocannabinoid system attenuate LID (Morgese et al ., ; González‐Aparicio & Moratalla, ; Martinez et al ., ; Dos‐Santos‐Pereira et al ., ). While the molecular mechanisms underlying the beneficial effects of endocannabinoid system on LID remain to be determined, the functional evaluation of cannabinoid receptors in astroglia may reveal their contribution.…”

Section: Non‐neuronal Mechanisms Of Dyskinesia: Astrocytesmentioning

confidence: 97%

l‐DOPA‐induced dyskinesia and neuroinflammation: do microglia and astrocytes play a role?

Carta

Mulas

Bortolanza

et al. 2016

Eur J of Neuroscience

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In Parkinson's disease (PD), L-DOPA therapy leads to the emergence of motor complications including L-DOPA-induced dyskinesia (LID). LID relies on a sequence of pre-and postsynaptic neuronal events, leading to abnormal corticostriatal neurotransmission and maladaptive changes in striatal projection neurons. In recent years, additional non-neuronal mechanisms have been proposed to contribute to LID. Among these mechanisms, considerable attention has been focused on L-DOPA-induced inflammatory responses. Microglia and astrocytes are the main actors in neuroinflammatory responses, and their double role at the interface between immune and neurophysiological responses is starting to be elucidated. Both microglia and astrocytes express a multitude of neurotransmitter receptors and via the release of several soluble molecules modulate synaptic function in neuronal networks. Here we review preclinical and clinical evidence of glial overactivation by L-DOPA, supporting a role of microglia and astrocytes in the development of LID. We propose that in PD, chronically and abnormally activated microglia and astrocytes lead to an aberrant neuron-glia communication, which affect synaptic activity and neuroplasticity contributing to the development of LID.

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“…Astrocytes contribute to brain endocannabinoid signaling by secreting 2-arachidonoylglycerol (2-AG; Navarrete, Díez, & Araque, 2014;Viader et al, 2015;Walter, Dinh, & Stella, 2004), a specific ligant of cannabinoid receptors type 1 (CB1) and type 2 (CB2) expressed in astrocytes and microglia. Anandamide, one of the most abundant endogenous cannabinoid in the basal ganglia, presents intrinsic anti-inflammatory properties and is related to L-DOPAinduced dyskinesia (Dos-Santos-Pereira, da-Silva, Guimarães, & Del-Bel, 2016;Fern andez-Ruiz, 2009;Johnston et al, 2011). The endocannabinoid system was proposed to be neuroprotective in different pathologies of the central nervous system (Grundy, Rabuffetti, & Beltramo, 2001;Mechoulam, 2002;van der Stelt et al, 2002).…”

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confidence: 99%

l-DOPA-induced dyskinesia in Parkinson's disease: Are neuroinflammation and astrocytes key elements?

Del‐Bel

Bortolanza

Pereira

et al. 2016

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Inflammation in Parkinson's disease (PD) is a new concept that has gained ground due to the potential of mitigating dopaminergic neuron death by decreasing inflammation. The solution to this question is likely to be complex. We propose here that the significance of inflammation in PD may go beyond the nigral cell death. The pathological process that underlies PD requires years to reach its full extent. A growing body of evidence has been accumulated on the presence of multiple inflammatory signs in the brain of PD patients even in very late stages of the disease. Because neuron-microglia-astrocyte interactions play a major role in the plasticity of neuronal response to l-DOPA in post-synaptic neurons, we focused this review on our recent results of l-DOPA-induced dyskinesia in rodents correlating it to significant findings regarding glial cells and neuroinflammation. We showed that in the rat model of PD/l-DOPA-induced dyskinesia there was an increased expression of inflammatory markers, such as the enzymes COX2 in neurons and iNOS in glial cells, in the dopamine-denervated striatum. The gliosis commonly seem in PD was associated with modifications in astrocytes and microglia that occur after chronic treatment with l-DOPA. Either as a cause, consequence, or promoter of progression of neuronal degeneration, inflammation plays a role in PD. The key aims of current PD research ought to be to elucidate (a) the time sequence in which the inflammatory factors act in PD patient brain and (b) the mechanisms by which neuroinflammatory response contributes to the collateral effects of l-DOPA treatment.

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Co-administration of cannabidiol and capsazepine reduces L-DOPA-induced dyskinesia in mice: Possible mechanism of action

Cited by 75 publications

References 137 publications

Bi‐directional modulation of food habit expression by the endocannabinoid system

Bi‐directional modulation of food habit expression by the endocannabinoid system

l‐DOPA‐induced dyskinesia and neuroinflammation: do microglia and astrocytes play a role?

l-DOPA-induced dyskinesia in Parkinson's disease: Are neuroinflammation and astrocytes key elements?

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