NeuropharmacologyCocaine reward and hyperactivity in the rat: Sites of mu opioid receptor modulation
Section snippets
Drugs
Cocaine HCl was generously provided by the National Institute on Drug Abuse (Bethesda, MD, USA), dissolved in sterile saline, and injected i.p. in a dose of 10 mg/kg and a volume of 1 ml/kg body weight. The dose is based on the weight of the salt. CTAP was obtained from Sigma, dissolved in sterile saline, and 0.5 μg in 0.5 μl was administered bilaterally into the brain regions of interest.
Animals and surgery
All animal procedures were approved by Temple University's Institutional Animal Care and Use Committee and
Effect of CTAP on the development of conditioned place preference
Conditioned place preference together with microinjections of the selective mu opioid receptor antagonist CTAP into five specific brain regions was employed to evaluate the role of mu opioid receptors within these regions in the development of cocaine reward. Fig. 1 shows termination sites of the tracts from the injection cannula for all regions studied. The data displayed in Fig. 2 represent the mean±S.D. in preference for the drug-paired environment for each of the five separate brain regions
Discussion
Previous studies using non-selective opioid receptor antagonists have shown that the opioid system plays a role in cocaine-induced reward (Bain and Kornetsky 1987, Corrigall and Coen 1991, Bilsky et al 1992) and hyperlocomotion (Houdi et al 1989, Kim et al 1997). In addition, a recent study by our laboratory has demonstrated that i.c.v. administration of the selective mu opioid receptor antagonist CTAP significantly attenuated acute cocaine-induced hyperactivity, and the development of
Conclusion
In summary, the results of the present study demonstrate the importance of mu opioid receptors in cocaine-induced reward and activity, and demonstrate the anatomical selectivity of mu receptors within the nucleus accumbens, VTA and caudate putamen in this regard. These data suggest that cocaine causes the release of endogenous opioid peptides and that these peptides contribute to the rewarding and locomotor-stimulating effects of cocaine. Further, the data also suggest that opioid peptides are
Acknowledgments
This work was supported by NIH/NIDA R01 DA09580 (E.M.U.). The authors would like to thank Peter Bugelski and Patricia Rafferty from Centocor Inc. Research and Development, for their expert guidance and training in immunohistochemistry.
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