title: Cannabinoid CB1 receptors activation and coactivation with D2 receptors modulate GABAergic neurotransmission in the globus pallidus and increase motor asymmetry.
abstract: The cannabinoid CB1 (CB1R) and dopaminergic D2 (D2R) receptors modify GABAergic transmission in the globus pallidus. Although dopaminergic denervation produces changes in the expression and supersensitization of these receptors, the consequences of these changes on GABAergic neurotransmission are unknown. The aim of this study was to show the effects of CB1R and D2R activation and coactivation on the uptake and release of [(3) H]GABA in the globus pallidus of hemiparkinsonian rats as well as their effects on motor behavior. The activation of CB1R blocked GABA uptake and decreased GABA release in the globus pallidus in the dopamine denervated side, whereas the co-activation of CB1R-D2R increased GABA release and had no effect on GABA uptake. A microinjection of the CB1R agonist ACEA into the globus pallidus ipsilaterally to a 6-OHDA lesion potentiated turning behavior that was induced by methamphetamine. However, a microinjection of the D2R agonist quinpirole did not modify this behavior, and a microinjection of a mixture of CB1R and D2R agonists significantly potentiated turning behavior. The behavioral effects produced after the activation of the CB1R and the co-activation of CB1R and D2R can be explained by increased GABAergic neurotransmission produced by a block of GABA uptake and an increase in the release of GABA in the globus pallidus, respectively.
authors.affiliation: Laboratorio de Neurofarmacología, Facultad de Ciencias Químicas, and Posgrado en Ciencias Químicas, Benemérita Universidad Autónoma de Puebla, Puebla, 72570, México.
authors.forename: Guadalupe
authors.initials: G
authors.lastname: Muñoz-Arenas
authors.forename: Francisco
authors.initials: F
authors.lastname: Paz-Bermúdez
authors.forename: Ana
authors.initials: A
authors.lastname: Báez-Cordero
authors.forename: René
authors.initials: R
authors.lastname: Caballero-Florán
authors.forename: Brenda
authors.initials: B
authors.lastname: González-Hernández
authors.forename: Benjamín
authors.initials: B
authors.lastname: Florán
authors.forename: I Daniel
authors.initials: ID
authors.lastname: Limón
mesh_terms: D000818:Animals; D001095:Arachidonic Acids / Q000494:pharmacology; D059330:GABAergic Neurons / Q000187:drug effects / Q000378:metabolism*; D005917:Globus Pallidus / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D008297:Male; D008694:Methamphetamine / Q000494:pharmacology; D009068:Movement; D016627:Oxidopamine / Q000633:toxicity; D019257:Quinpirole / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D043884:Receptor, Cannabinoid, CB1 / Q000819:agonists / Q000378:metabolism*; D017448:Receptors, Dopamine D2 / Q000819:agonists / Q000378:metabolism*; D009435:Synaptic Transmission; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D001095:Arachidonic Acids; D043884:Receptor, Cannabinoid, CB1; D017448:Receptors, Dopamine D2; C119325:arachidonyl-2-chloroethylamide; D019257:Quinpirole; D008694:Methamphetamine; D005680:gamma-Aminobutyric Acid; D016627:Oxidopamine
keywords: GABA release; GABA uptake; cannabinoid CB1 receptor; dopaminergic D2 receptor; globus pallidus; motor asymmetry