This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. The goal of this research award has been restructured to investigate the modulatory impact of serotonin (5-HT) 2-subtype receptor activation or blockade upon the behavioral and neurochemical effects of cocaine in nonhuman primates, with an emphasis upon medications development for the treatment of cocaine abuse. To date, we have found that pharmacological activation of the 5-HT2C-subtype receptor attenuates the behavioral-stimulant and neurochemical effects of cocaine. Additionally, the selective 5-HT2C receptor agonist Ro 60-0175 has been shown to selectively reduce the reinforcing and relapse-inducing effects of cocaine in procedures that model drug use and relapse. In contrast, the selective 5-HT2C receptor antagonist SB 242084 has been found to generate behavioral effects suggestive of a modest stimulant-like profile, and also potentiate the behavioral and neurochemical effects of cocaine. Finally, the 5-HT2A-subtype receptor antagonist has not demonstrated the capacity to modulate the behavioral effects of cocaine, in contrast to findings from rodent studies. The results thus far indicate that 5-HT2C receptor agonists may represent a novel pharmacotherapeutic drug class for the treatment of cocaine abuse.
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