Dopamine D1 receptor-expressing neurons activity is essential for locomotor and sensitizing effects of a single injection of cocaine.
Eur J Neurosci
; 54(4): 5327-5340, 2021 08.
Article
em En
| MEDLINE
| ID: mdl-34273137
ABSTRACT
Dopamine D1 receptors play an important role in the effects of cocaine. Here, we investigated the role of neurons which express these receptors (D1-neurons) in the acute locomotor effects of cocaine and the locomotor sensitization observed after a second injection of this drug, using the previously established two-injection protocol of sensitization. We inhibited D1-neurons using double transgenic mice conditionally expressing the inhibitory Gi-coupled designer receptor exclusively activated by designer drugs (Gi-DREADD) in D1-neurons. Chemogenetic inhibition of D1-neurons by a low dose of clozapine (0.1 mg/kg) decreased the cocaine-induced expression of Fos in striatal neurons. It diminished the basal locomotor activity and acute hyper-locomotion induced by cocaine (20 mg/kg). Clozapine 0.1 mg/kg had no effect by itself and did not alter cocaine effects in wild-type mice. Inhibition of D1-neurons during the first cocaine administration prevented the sensitization of the locomotor response in response to a second cocaine administration 10 days later. On Day 11, inhibition of D1-neurons by clozapine stimulation of Gi-DREADD blocked cocaine-induced locomotion including in sensitized mice, whereas on Day 12, in the absence of clozapine and D1-neurons inhibition, all mice displayed a sensitized response to cocaine. These results show that chemogenetic inhibition of D1-neurons decreases spontaneous and cocaine-induced locomotor activity. It prevents sensitization induction and blocks sensitized locomotion in a two-injection protocol of sensitization but does not reverse established sensitization. Our study further supports the central role of D1-neurons in mediating the acute locomotor effects of cocaine and its sensitization.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Cocaína
Limite:
Animals
Idioma:
En
Revista:
Eur J Neurosci
Assunto da revista:
NEUROLOGIA
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
França