Abstract
In previous studies, heroin was shown to engender cocaine-like discriminative stimulus (DS) effects; however, the mechanisms underlying the cocaine-like effects of heroin are unknown. The present study evaluated the extent to which the shared DS effects of heroin and cocaine involve common monoaminergic mechanisms of action. In squirrel monkeys discriminating cocaine (0.3 mg/kg) from saline, heroin engendered full or partial substitution for cocaine in three of four monkeys. Pretreatment with the selective dopamine transport inhibitor 1-(2-[bis(4-fluorophenyl)methoxy]ethyl)-4-(3-phenylpropyl)piperazine (GBR 12909) dose dependently enhanced the cocaine-like DS effects of heroin in these three monkeys as well as the DS effects of cocaine in all subjects. Neither talsupram, a noradrenergic transport inhibitor, nor prazosin, a noradrenergic antagonist selective for α-1 receptors, systematically altered the cocaine-like DS effects of heroin at doses that enhanced (talsupram) or attenuated (prazosin) the DS effects of cocaine. Pretreatment with the serotonin uptake inhibitor citalopram similarly failed to alter the cocaine-like DS effects of heroin at doses that attenuated the DS effects of cocaine. Altogether, these findings suggest that heroin shares DS effects with cocaine in a subset of monkeys, and these cocaine-like effects are mediated at least in part by enhanced dopaminergic activity. Unlike the DS effects of cocaine itself, however, the cocaine-like DS effects of heroin do not appear to involve either noradrenergic or serotonergic mechanisms.
Footnotes
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This study was supported by U.S. Public Health Service Grants DA11928, DA00499, and RR00168.
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DOI: 10.1124/jpet.104.065631.
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ABBREVIATIONS: DA, dopamine; CI, confidence interval; DAT, dopamine transporter; DS, discriminative stimulus; GBR 12909, 1-(2-[bis(4-fluorophenyl)methoxy]ethyl)-4-(3-phenylpropyl)piperazine; NE, norepinephrine; NET, norepinephrine transporter; SERT, serotonin transporter; 5-HT, 5-hydroxytryptamine; FR, fixed ratio.
- Received January 18, 2004.
- Accepted February 24, 2004.
- The American Society for Pharmacology and Experimental Therapeutics
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