Effects of ifenprodil on stimulatory, discriminative stimulus, and convulsant effects of cocaine

Ifenprodil, like cocaine, binds to the dopamine transporter and blocks uptake of dopamine. In this study, the ability of ifenprodil to mimic, enhance or block behavioral and toxic effects of cocaine was evaluated. Fixed-interval responding maintained by food presentation in rats was increased by cocaine but decreased by ifenprodil. Low rates of responding during timeout periods were also increased by cocaine but not ifenprodil. Ifenprodil neither increased locomotor activity nor augmented the stimulatory effect of cocaine; however, ifenprodil attenuated the stimulant effects of cocaine at doses 0.5 log unit lower than those required to reduce spontaneous activity when given alone. Ifenprodil neither substituted for nor augmented the discriminative stimulus effects of cocaine in rats discriminating 10mg/kg cocaine from saline. In contrast to cocaine, ifenprodil did not produce convulsions or signs of proconvulsant activity, and ifenprodil reduced the percentage of mice convulsing in the presence of cocaine. These results suggest that pharmacological actions in addition to blockade of dopamine uptake or novel interactions with the dopamine transporter may contribute to the non-stimulant behavioral profile and cocaine-blocking actions of ifenprodil.