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|Title:||THE ROLE OF DOPAMINE IN ACUTE FOOD DEPRIVATION-INDUCED REINSTATEMENT OF HEROIN SEEKING|
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|Authors/Affiliations:||1 Stephanie Tobin*; 2 Amy H Newman; 1 Tammie Quinn; 1 Uri Shalev; |
1 Department of Psychology, Center for Studies in Behavioral Neurobiology, Concordia University, Montreal, QC, Canada; 2 National Institute on Drug Abuse, National Institutes of Health, DHHS, Baltimore, MD, USA
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|Content:||Rational and Objectives: Using the reinstatement procedure, an animal model of drug relapse in humans, dopamine (DA) has been shown to play a significant role in the reinstatement of drug seeking due to priming or drug cue presentations. However, DA is suggested to play a limited role in stress-induced reinstatement, as modelled by footshock stress. Unlike footshock, however, acute food deprivation (FD) stress reinstates heroin seeking in rats via a leptin dependent mechanism. This mechanism may function through the modulation of DA transmission. Thus, we have chosen to reassess the role of DA in stress-induced reinstatement using acute FD stress.|
Materials and Methods: Rats were trained to self-administer heroin (0.05 mg/kg/infusion) over a period of 10 days (days 1-5: 3 X 3 h sessions; days 6-10: 1 X 3 h session). Heroin-seeking behavior was extinguished by removing the drug. Following a minimum of 4 days of extinction, rats were tested for reinstatement, ad Libitum or following 48 h food deprivation, while pre-treated with the specific DA D1, D2, or D3 receptor antagonists: SCH 23390 (0.0, 5.0 and 10.0 µg/kg), raclopride (0.0, 50.0 and 100.0 µg/kg) or NGB 2904 (0.0, 0.1 and 5.0 mg/kg). Using a similar procedure the effects of raclopride and NGB 2904 on cue-induced reinstatement were assessed separately in different groups of rats.
Results: A dose-dependent attenuation of FD-induced reinstatement was apparent in rats given the DA D1 receptor antagonist SCH 23309; but, not the DA D2 or D3 receptor antagonists raclopride or NGB 2904. Raclopride (100.0 µg/kg), but not NGB 2904 (5.0 mg/kg), did however attenuate cue-induced reinstatement.
Conclusion: The results of this study suggest an involvement of the DA D1 receptor in mediating acute 48h FD-induced reinstatement. The non-significant effect of raclopride and NGB 2904 suggests that an activation of the DA D2 or D3 receptors is not involved in FD-induced reinstatement. Previously, systemic injection of SCH 23390 has been shown to have no effect on footshock-induced reinstatement. Thus, our present findings suggest that DA transmission may play a differential role in footshock and acute FD-induced reinstatement.
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