Dopamine beta-hydroxylase-deficient mice have normal densities of D(2) dopamine receptors in the high-affinity state based on in vivo PET imaging and in vitro radioligand binding.
Synapse
; 64(9): 699-703, 2010 Sep.
Article
en En
| MEDLINE
| ID: mdl-20336622
In vitro, D(2) dopamine receptors (DAR) can exist in low- and high-affinity states for agonists and increases of D(2) receptors in high-affinity state have been proposed to underlie DA receptor supersensitivity in vivo. Deletion of the gene for dopamine beta-hydroxylase (DBH) causes mice to become hypersensitive to the effects of psychostimulants, and in vitro radioligand binding results suggest an increased percentage of D(2) receptors in a high-affinity state. To determine whether DBH knockout mice display an increase of high-affinity state D(2) receptors in vivo, we scanned DBH knockout and control mice with the agonist PET radioligand [(11)C]MNPA, which is thought to bind preferentially to the high-affinity state of the D(2) receptor. In addition, we performed in vitro binding experiments on striatal homogenates with [(3)H]methylspiperone to measure B(max) values and the percentages of high- and low-affinity states of the D(2) receptor. We found that the in vivo striatal binding of [(11)C]MNPA was similar in DBH knockout mice and heterozygous controls and the in vitro B(max) values and percentages of D(2) receptors in the high-affinity state, were not significantly different between these two groups. In summary, our results suggest that DBH knockout mice have normal levels of D(2) receptors in the high-affinity state and that additional mechanisms contribute to their behavioral sensitivity to psychostimulants.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Receptores de Dopamina D2
/
Dopamina beta-Hidroxilasa
Límite:
Animals
Idioma:
En
Revista:
Synapse
Asunto de la revista:
NEUROLOGIA
Año:
2010
Tipo del documento:
Article
País de afiliación:
Estados Unidos
Pais de publicación:
Estados Unidos