Modulation of striatal dopamine dynamics by cocaine self-administration and amphetamine treatment in female rats.
Eur J Neurosci
; 50(4): 2740-2749, 2019 08.
Article
em En
| MEDLINE
| ID: mdl-31111573
ABSTRACT
Despite decades of research into the neurobiological basis of cocaine abuse, pharmacotherapeutic treatments for cocaine addiction have been largely ineffective. Converging evidence from preclinical research and from outpatient clinical trials suggest that treatment with amphetamine is efficacious in reducing cocaine intake. Although it has been suggested that amphetamine treatment reduces cocaine intake as an agonist replacement therapy, we have shown recently that multiple aspects of dopamine signaling are altered by cocaine self-administration and returned to pre-cocaine function by amphetamine treatment in the nucleus accumbens of male rats. Here, we sought to determine if these effects were also evident in female subjects, and across regions of the striatum. Female rats performed 5 days of cocaine self-administration (1.5 mg kg-1 inj-1 , 40 inj/day) and were treated with a single amphetamine (0.56 mg/kg) or saline infusion 1 hr prior to killing. We then used ex vivo fast-scan cyclic voltammetry in the nucleus accumbens core or dorsolateral caudate-putamen to examine dopamine signaling and cocaine potency. We found that in the nucleus accumbens core, cocaine self-administration decreased dopamine uptake rate and cocaine potency, and both alterations were restored by amphetamine treatment. In the dorsolateral caudate-putamen, neither cocaine self-administration nor amphetamine treatment altered dopamine uptake; however, cocaine potency was decreased by self-administration and returned to control levels by amphetamine. Together, these findings support a role for amphetamine treatment for cocaine addiction outside of agonist replacement therapy, and suggest that the development of cocaine tolerance is similar across sexes.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Dopamina
/
Cocaína
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Inibidores da Captação de Dopamina
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Transtornos Relacionados ao Uso de Cocaína
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Corpo Estriado
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Anfetamina
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Estimulantes do Sistema Nervoso Central
Limite:
Animals
Idioma:
En
Revista:
Eur J Neurosci
Assunto da revista:
NEUROLOGIA
Ano de publicação:
2019
Tipo de documento:
Article