SEPARATION OF THE LOCOMOTOR STIMULANT AND DISCRIMINATIVE STIMULUS EFFECTS OF COCAINE BY ITS C-2 PHENYL ESTER ANALOG, RTI-15

During a routine evaluation of several analogs of cocaine, we observed that the C-2 phenyl ester, RTI-15, appeared to suppress motor activit y in rats. We subsequently examined RTI-15 for its cocaine-like stimul us effects as well as for its locomotor activity effects. RTI-15 dose- dependently generalized from the cocaine stimulus in rats trained to d iscriminate 10 mg/kg cocaine from saline with complete substitution (g reater than or equal to 80% cocaine-lever responding) occurring at 24 mg/kg. During automated locomotor activity tests in mice, cocaine (3-6 0 mg/kg) dose-dependently increased activity counts and movement time across the entire 1 h test session. RTI-15, however, had little affect on activity counts and movement time from 10-30 mg/kg, and decreased these measures at 60 mg/kg, the highest dose tested. These results ind icate that while changing the C-2 methyl ester of cocaine to a C-2 phe nyl ester increases dopamine-transporter selectivity, it dissociates i ts locomotor activity effects from its discriminative stimulus effects suggesting that the underlying mechanisms mediating these effects are not identical. (C) 1998 Elsevier Science Ireland Ltd. All rights rese rved.