Enhanced vulnerability to cocaine self-administration is associated with elevated impulse activity of midbrain dopamine neurons.
J Neurosci
; 20(23): 8876-85, 2000 Dec 01.
Article
em En
| MEDLINE
| ID: mdl-11102497
ABSTRACT
Individual differences in responding to a novel environment predict behavioral and neurochemical responses to psychostimulant drugs. Rats with a high locomotor response to a novel environment (HRs) exhibit enhanced self-administration (SA) behavior, sensitization, and basal or drug-induced dopamine release in the nucleus accumbens compared with rats with a low response to the novel context (LRs). In this study, we determined whether such differences in vulnerability to drug addiction might be related to differences in dopamine (DA) neuron activity. Rats were divided into HRs and LRs according to their response to a novel environment and then tested for acquisition of cocaine SA. HRs rapidly acquired cocaine SA (175 microg/kg per infusion), whereas LRs did not. Differences in cocaine SA were not caused by differences in exploratory behavior or sampling because these behaviors did not differ in HRs and LRs self-administering a saline solution. In a separate experiment, we used extracellular single-unit recordings and found that HRs exhibit higher basal firing rates and bursting activity of DA neurons in the ventral tegmental area and, to a lesser extent, in the substantia nigra pars compacta. The greater activity of midbrain DA cells in HRs was accompanied by reduced sensitivity to the inhibitory effects of a DA D2-class receptor agonist, indicating possible subsensitivity of impulse-regulating DA autoreceptors. These results demonstrate that differences in the basal activity of DA neurons may be critically involved in determining individual vulnerability to drugs of abuse.
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Mesencéfalo
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Dopamina
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Cocaína
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Transtornos Relacionados ao Uso de Cocaína
/
Neurônios
Tipo de estudo:
Risk_factors_studies
Limite:
Animals
Idioma:
En
Revista:
J Neurosci
Ano de publicação:
2000
Tipo de documento:
Article
País de afiliação:
Estados Unidos