Behavioural and anatomical characterization of mutant mice with targeted deletion of D1 dopamine receptor-expressing cells: response to acute morphine.
J Pharmacol Sci
; 121(1): 39-47, 2013.
Article
en En
| MEDLINE
| ID: mdl-23337398
ABSTRACT
Considerable topographic overlap exists between brain opioidergic and dopaminergic neurons. Pharmacological blockade of the dopamine D(1) receptor (Drd1a) reverses several behavioural phenomena elicited by opioids. The present study examines the effects of morphine in adult mutant (MUT) mice expressing the attenuated diphtheria toxin-176 gene in Drd1a-expressing cells, a mutant line shown previously to undergo post-natal striatal atrophy and loss of Drd1a-expression. MUT and wild-type mice were assessed behaviourally following acute administration of 10 mg/kg morphine. Treatment with morphine reduced locomotion and rearing similarly in both genotypes but reduced total grooming only in MUT mice. Morphine-induced Straub tail and stillness were heightened in MUT mice. Chewing and sifting were decreased in MUT mice and these effects were not modified by morphine. Loss of striatal Drd1-positive cells and up-regulated D(2)-expression, as reflected in down-regulated D(1)-like and up-regulated D(2)-like binding, respectively, is not uniform along the cranio-caudal extent in this model but appears to be greater in the caudal striatum. Preferential caudal loss of µ-opioid-expression, a marker for the striosomal compartment, was seen. These data indicate that Drd1a-positive cell loss modifies the exploratory behavioural response elicited by morphine, unmasking novel morphine-induced MUT-specific behaviours and generating a hypersensitivity to morphine for others.
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Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Conducta Animal
/
Receptores de Dopamina D1
/
Ratones Mutantes
/
Morfina
Límite:
Animals
Idioma:
En
Revista:
J Pharmacol Sci
Asunto de la revista:
FARMACOLOGIA
Año:
2013
Tipo del documento:
Article
País de afiliación:
Irlanda