Cocaine-like discriminative stimulus effects of heroin: modulation by selective monoamine transport inhibitors.
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 alpha-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.
Harvard Medical School, New England Primate Research Center, Southborough, Massachusetts 01772-9102, USA. james_rowlett@hms.harvard.edu
James K
JK
Rowlett
Donna M
DM
Platt
Roger D
RD
Spealman
D000818:Animals; D002352:Carrier Proteins / Q000502:physiology; D015283:Citalopram / Q000494:pharmacology; D003042:Cocaine / Q000494:pharmacology*; D004192:Discrimination, Psychological / Q000187:drug effects*; D050483:Dopamine Plasma Membrane Transport Proteins; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D004347:Drug Interactions; D003932:Heroin / Q000494:pharmacology*; D008297:Male; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000502:physiology; D026901:Membrane Transport Proteins / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism / Q000502:physiology; D009479:Neuropeptides; D050484:Norepinephrine Plasma Membrane Transport Proteins; D010879:Piperazines / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D018340:Receptors, Adrenergic, alpha-1 / Q000502:physiology; D012453:Saimiri; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology; D027981:Symporters / Q000502:physiology; D013876:Thiophenes / Q000494:pharmacology; D050492:Vesicular Biogenic Amine Transport Proteins
D002352:Carrier Proteins; D015283:Citalopram; D003042:Cocaine; D050483:Dopamine Plasma Membrane Transport Proteins; D018765:Dopamine Uptake Inhibitors; D003932:Heroin; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D009479:Neuropeptides; D050484:Norepinephrine Plasma Membrane Transport Proteins; D010879:Piperazines; D011224:Prazosin; D018340:Receptors, Adrenergic, alpha-1; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors; D027981:Symporters; D013876:Thiophenes; D050492:Vesicular Biogenic Amine Transport Proteins; C043425:vanoxerine; C001750:talsupram