Pharmacological activation of dopamine D4 receptor modulates morphine-induced changes in the expression of GAD65/67 and GABAB receptors in the basal ganglia.
Neuropharmacology
; 152: 22-29, 2019 07 01.
Article
en En
| MEDLINE
| ID: mdl-30682345
ABSTRACT
Dopamine D4 receptor (D4R) stimulation, in a putative D4R/µ opioid heteroreceptor (MOR) complex, counteracts the molecular, cellular and behavioural actions of morphine which are associated with morphine addiction, without any effect on its analgesic properties. In the present work, we have evaluated the role of D4R in modulating the effects of a continuous treatment with morphine on the GABAergic system in the basal ganglia. It has been demonstrated that the co-administration of a D4R agonist together with morphine leads to a restoration of GABA signaling by preventing drug-induced changes in GAD65/67 expression in the caudate putamen, globus palidus and substantia nigra. Results from GABABR1 and GABABR2 expression suggest a role of D4R in modulation of the GABAB heteroreceptor complexes along the basal ganglia, especially in the functional divisions of the caudate putamen. These results provide a new proof of the functional interaction between D4R and MOR and we postulate this putative heteroreceptor complex as a key target for the development of a new strategy to prevent the addictive effects of morphine in the treatment of pain. This article is part of the Special Issue entitled 'Receptor heteromers and their allosteric receptor-receptor interactions'.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Receptores de GABA-B
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Receptores de Dopamina D4
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Glutamato Descarboxilasa
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Morfina
Límite:
Animals
Idioma:
En
Revista:
Neuropharmacology
Año:
2019
Tipo del documento:
Article
Pais de publicación:
ENGLAND
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ESCOCIA
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GB
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GREAT BRITAIN
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INGLATERRA
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REINO UNIDO
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SCOTLAND
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UK
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UNITED KINGDOM