The endogenous cannabinoid receptor ligand, anandamide, inhibits the motor behavior: role of nigrostriatal dopaminergic neurons

Romero, Julián; García, Laura Pérez; Cebeira, M.; Zadrożny, Dariusz; Fernández‐Ruiz, Javier; Ramos, J.A.

doi:10.1016/0024-3205(95)00186-a

Cited by 99 publications

(50 citation statements)

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“…Specific stereotypies are mediated by specific regions within the striatum by an interaction between D1-type and D2-type DA receptors (Cameron and Crocker 1989;Kelly et al 1975;Romero et al 1995;Schmidt 1986). Whereas locomotion and head and sniffing stereotypies are mediated by a number of sub-circuits in dorsal and ventral striatum (Delfs and Kelley 1990;Koene et al 1993;Cameron and Crocker 1989;Schmidt 1986), oral stereotypies such as biting and licking are regulated primarily by the medial or lateral ventral striatum (Delfs and Kelley 1990;Downes and Waddington 1993;Koene et al 1993).…”

Section: The Pharmacology Of the Apo-induced Stereotypies Blocked By mentioning

confidence: 99%

A Role for Electrotonic Coupling in the Striatum in the Expression of Dopamine Receptor-mediated Stereotypies,

Moore

Grace

2002

Neuropsychopharmacology

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Stimulation of dopamine (DA) receptors in the striatum evokes a number of alterations in motor behavior in rats, as well as causing several alterations in cellular physiology, including changes in membrane potential, cell excitability, afferent drive, and electrotonic coupling. One cellular property that is potently modulated by DA stimulation is electrotonic coupling, a process shown to subserve motor pattern generation. To examine whether electrotonic coupling plays a role in mediating a specific set of DA receptor-mediated motor behaviors, we tested the effects of two inhibitors of gap junction conductance, carbenoxolone (CARB) and anandamide (AEA), on apomorphine (APO)-induced motor responses. We then used intra-striatal infusions of CARB to determine the role of electrotonic coupling specifically in the ventral striatum in the expression of i.p.) significantly increased motor activity (a composite score) and the frequencies of oral and sniffing stereotypies. APO also disrupted grooming initiation and completion. APO-induced oral stereotypies were selectively blocked by systemic administration of CARB (7.0, 35.0 mg/kg Adaptive behaviors, both learned and spontaneous, consist of sequences of "micro" movements executed by closely-related muscle groups. There is evidence that the initiation and execution of individual movements, such as oral movements involved in feeding, as well as the linking of these movements into a behavioral sequence, depend upon neuronal networks within the Beninger et al. 1991;Braun and Chase 1986;Byrnes et al. 1994;Delfs and Kelley 1990). Thus, in the context of behavioral sequencing, the simple 'repetitive' stereotypy (Berridge and Aldridge 2000a) produced by D2 receptor over-stimulation in the striatum (Delfs and Kelley 1990) can be seen as the inability to release one 'simple' behavior in order to allow initiation of the next simple behavior in a normal, adaptive sequence (Pedro et al. 1994;Szechtman et al. 1999). One means by which neuronal networks may interact within the striatum is via communication among clusters of functionally related striatal neurons. Such a network interaction may be mediated via gap junctions. It is well-established that electrotonic transmission between developing neurons is important in the formation and stabilization of functional networks (Bannerman et al. 2000;Peinado et al. 1993;Roerig and Feller 2000). However, there is also evidence that in the adult brain, electrotonic coupling directly mediates forms of neuronal network activity (Bou-Flores and Berger 2001;Jefferys 1995;Perez Velazquez and Carlen 2000) which, in turn, contribute to rhythmic behavioral patterning (Bou-Flores and Berger 2001;Rothwell 1998). Thus, it is likely that motor patterning may involve activity within neuronal networks coordinated via gap junctions. In the striatum, cells express connexins, the protein building blocks of gap junctions (Belluardo et al. 2000;Bennett et al. 1999). Striatal neurons also exhibit dye coupling, the transfer of dye molecules between neurons thro...

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Section: The Pharmacology Of the Apo-induced Stereotypies Blocked By mentioning

confidence: 99%

A Role for Electrotonic Coupling in the Striatum in the Expression of Dopamine Receptor-mediated Stereotypies,

Moore

Grace

2002

Neuropsychopharmacology

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“…9 Intraperitoneal administration of anandamide, the natural ligand of CB1 receptor, in rats causes a significant decrease in tyrosine hydroxylase and a decrease in the ratio of D1 and D2 receptors in the striatum. 10 In reverse, interruption of DA neurotransmission by 6-hydroxydopamine lesions results in a 45% increase in cannabinoid receptor mRNA level in rats caudate. 11 The synthetic cannabinoid agonist, HU210, provokes relapse to cocaine seeking, and the selective CB1 receptor antagonist, SR141716A, attenuates relapse induced by re-exposure to cocaine-associated cues or by cocaine itself in an animal model of addiction.…”

Section: Introductionmentioning

confidence: 99%

(AAT)n repeat in the cannabinoid receptor gene (CNR1): association with cocaine addiction in an African-Caribbean population

et al. 2005

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Owing to their agonist action on dopaminergic systems, cannabinoids may play a major role in substance dependency and schizophrenia. We examined the (AAT)n triplet repeat polymorphism nearby the CNR1 gene, which encodes human cannabinoid (CB1) receptor, in a male Afro-Caribbean population. The allelic and genotypic distributions were significantly different in non-schizophrenic cocaine dependents (n ¼ 97), schizophrenic cocaine dependents (n ¼ 45) and matched controls (n ¼ 88) (Po10 À4 ). The frequency of the (AAT)12 repeat allele was increased in non-schizophrenic cocaine dependents and schizophrenic cocaine dependents vs controls (25.3 and 26.7 vs 5.7%) (Po10 À4 ). Our results support that the (AAT)n polymorphism nearby the CNR1 gene could be associated with predisposition to cocaine dependency.

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“…For example, studies have shown an increase in dopamine turnover and release after cannabinoid CB1 receptor stimulation of the striatum (Romero et al, 1995;Szabo et al, 1999) and stimulation of rat striatal D2 receptors in vivo triggers the release of the endocannabinoid anandamide. In turn, the released anandamide inhibits the facilitatory role on movement derived from dopamine D2 receptor stimulation (Giuffrida et al, 1999;Beltramo et al, 2000).…”

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confidence: 99%

Concurrent Stimulation of Cannabinoid CB1 and Dopamine D2 Receptors Enhances Heterodimer Formation: A Mechanism for Receptor Cross-Talk?

Kearn

Blake-Palmer²,

Daniel³

et al. 2005

Mol Pharmacol

311

268

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Dopamine and endogenous cannabinoids display complex interactions in the basal ganglia. One possible level of interaction is between CB1 cannabinoid and D2 dopamine receptors. Here, we demonstrate that a regulated association of CB1 and D2 receptors profoundly alters CB1 signaling. This provides the first evidence that CB1/D2 receptor complexes exist, are dynamic, and are agonist-regulated with highest complex levels detected when both receptors are stimulated with subsaturating concentrations of agonist. The consequence of this interaction is a differential preference for signaling through a "nonpreferred" G protein. In this case, D2 receptor activation, simultaneously with CB1 receptor stimulation, results in the receptor complex coupling to G␣s protein in preference to the expected G␣i/o proteins. The result of this interaction is an increase in the second messenger cAMP, reversing an initial synergistic inhibition of adenylyl cyclase activity seen at subthreshold concentrations of cannabinoid agonist. Additionally, a pertussis toxin insensitive component in the activation of extracellular signal-regulated kinase (ERK) 1/2 kinases by the cannabinoid agonist CP 55,940 [(1R,3R,4R)-3-[2-hydroxy-4-(1,1-dimethylheptyl)phenyl]-4-(3-hydroxypropyl)cyclohexan-1-ol] is revealed in cells stably expressing both CB1 and D2 receptors. Thus, concurrent receptor stimulation promotes a heterooligomeric receptor complex and an apparent shift of CB1 signaling from a pertussis toxin-sensitive inhibition to a partly pertussis toxin-insensitive stimulation of adenylyl cyclase and ERK 1/2 phosphorylation.

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The endogenous cannabinoid receptor ligand, anandamide, inhibits the motor behavior: role of nigrostriatal dopaminergic neurons

Cited by 99 publications

References 21 publications

A Role for Electrotonic Coupling in the Striatum in the Expression of Dopamine Receptor-mediated Stereotypies,

A Role for Electrotonic Coupling in the Striatum in the Expression of Dopamine Receptor-mediated Stereotypies,

(AAT)n repeat in the cannabinoid receptor gene (CNR1): association with cocaine addiction in an African-Caribbean population

Concurrent Stimulation of Cannabinoid CB1 and Dopamine D2 Receptors Enhances Heterodimer Formation: A Mechanism for Receptor Cross-Talk?

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