Journal
PLOS ONE
Volume 8, Issue 11, Pages -Publisher
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pone.0078258
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Funding
- CU Innovative Seed Grant
- [R03 DA 029420]
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The activation of dopamine receptors within the mesolimbic dopamine system is known to be involved in the initiation and maintenance of cocaine use. Expression of the D-2 dopamine receptor subtype has been implicated as both a predisposing factor and consequence of chronic cocaine use. It is unclear whether there is a predictive relationship between D-2 dopamine receptor function and cocaine sensitivity that would enable cocaine abuse. Therefore, we exploited individual differences in behavioral responses to D2 dopamine receptor stimulation to test its relationship with cocaine-mediated behaviors. Outbred, male Sprague-Dawley rats were initially characterized by their locomotor responsiveness to the D-2 dopamine receptor agonist, quinpirole, in a within-session ascending dose-response regimen (0, 0.1, 0.3 & 1.0 mg/kg, sc). Rats were classified as high or low quinpirole responders (HD2 and LD2, respectively) by a median split of their quinpirole-induced locomotor activity. Rats were subsequently tested for differences in the psychostimulant effects of cocaine by measuring changes in cocaine-induced locomotor activity (5 and 15 mg/kg, ip). Rats were also tested for differences in the development of conditioned place preference to a low dose of cocaine (7.5mg/kg, ip) that does not reliably produce a cocaine conditioned place preference. Finally, rats were tested for acquisition of cocaine self-administration and maintenance responding on fixed ratio 1 and 5 schedules of reinforcement, respectively. Results demonstrate that HD2 rats have enhanced sensitivity to the locomotor stimulating properties of cocaine, display greater cocaine conditioned place preference, and self-administer more cocaine compared to LD2 animals. These findings suggest that individual differences in D-2 dopamine receptor sensitivity may be predictive of cocaine sensitivity and reward.
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