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Modulation of Heroin and Cocaine Self-Administration by Dopamine D1- and D2-Like Receptor Agonists in Rhesus Monkeys
Cocaine-heroin combinations (âspeedballsâ) are commonly self-administered by polydrug abusers. Speedball self-administration may reflect in part an enhancement of the reinforcing effects of the drug combination compared with either drug alone. The present study investigated the degree to which t...
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Published in: | The Journal of pharmacology and experimental therapeutics 2007-06, Vol.321 (3), p.1135-1143 |
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Main Authors: | , , , |
Format: | Article |
Language: | English |
Subjects: | |
Citations: | Items that this one cites Items that cite this one |
Online Access: | Get full text |
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Summary: | Cocaine-heroin combinations (âspeedballsâ) are commonly self-administered by polydrug abusers. Speedball self-administration
may reflect in part an enhancement of the reinforcing effects of the drug combination compared with either drug alone. The
present study investigated the degree to which the dopamine receptor system plays a role in cocaine-induced enhancement of
heroin self-administration. In rhesus monkeys trained under a progressive ratio schedule of i.v. drug injection, combining
heroin with cocaine shifted the heroin dose-response function leftward, and isobolographic analysis indicated that the combined
effects were dose-additive. Likewise, combining heroin with the D1-like receptor agonists 6-chloro-7,8-dihydroxy-1-phenyl-2,3,4,5-tetrahydro-(1 H )-3-benzazepine HCl (SKF 81297) and 6-chloro- N -allyl-7,8-dihydroxy-1-phenyl-2,3,4,5-tetrahydro-[1 H ]-3-benzazepine (SKF 82958) resulted in a leftward shift in the heroin dose-response function that was dose-additive. In contrast,
combining heroin with the D2-like agonists R -(-)-propylnorapomorphine (NPA) and quinpirole shifted the heroin dose-response function to the right. Isobolographic analysis
of the combined effects of heroin with NPA and quinpirole revealed infra-additive interactions in both cases. When combined
with cocaine instead of heroin, both the D1-like receptor agonist SKF 81297 and the D2-like receptor agonist NPA enhanced
cocaine self-administration. The combinations of SKF 81297 with cocaine were dose additive; however, the NPA-cocaine interaction
was infra-additive. Together, the results suggest that D1- and D2-like receptor mechanisms may play qualitatively different
roles in the combined self-administration of heroin and cocaine. In particular, stimulation of D1-like receptors enhances
self-administration of heroin or cocaine individually, similar to the effects of combining cocaine with heroin, whereas stimulation
of D2-like receptors seems to play primarily an inhibitory role. |
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ISSN: | 0022-3565 1521-0103 |
DOI: | 10.1124/jpet.107.120766 |