Separation of the locomotor stimulant and discriminative stimulus effects of cocaine by its C-2 phenyl ester analog,RTI-15 |
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| Affiliation: | 1. Department of Psychology, CB No. 3270, Davie Hall, University of North Carolina, Chapel Hill, North Carolina 27599-3270, USA;2. Research Triangle Institute, 3040 Cornwallis Rd., P.O. Box 12194, Research Triangle Park, North Carolina 27709, USA;3. Medical College of Virginia, Department of Pharmacology and Toxicology, 410 N. 12th St., Smith Building No. 756A, Box 980613, Richmond, VA 23298-0613, USA;1. Computer-Aided Drug Design Center, Department of Pharmaceutical Sciences, School of Pharmacy, University of Maryland, Baltimore, MD 21201, United States;2. Life Sciences Department, Barcelona Supercomputing Center, Jordi Girona 29, Barcelona 08034, Spain;3. Department of Analytical Chemistry and Pharmaceutical Technology (FABI), Center for Pharmaceutical Research (CePhaR), Vrije Universiteit Brussel (VUB), Laarbeeklaan 103, B-1090 Brussels, Belgium;4. Department of Chemistry and Biophysics, University of Michigan, 930 North University Avenue, Ann Arbor, MI 48109, United States;1. Division of General Internal Medicine, Section of Addiction Medicine, Oregon Health & Science University, Portland, OR, United States;2. Central City Concern, Portland, OR, United States;3. Evidence Synthesis Program Center, VA Portland Health Care System, Portland, OR, United States;4. Department of Medicine, VA Portland Health Care System, Portland, OR, United States |
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| Abstract: | During a routine evaluation of several analogs of cocaine, we observed that the C-2 phenyl ester, RTI-15, appeared to suppress motor activity in rats. We subsequently examined RTI-15 for its cocaine-like stimulus effects as well as for its locomotor activity effects. RTI-15 dose-dependently generalized from the cocaine stimulus in rats trained to discriminate 10 mg/kg cocaine from saline with complete substitution (⩾80% cocaine-lever responding) occurring at 24 mg/kg. During automated locomotor activity tests in mice, cocaine (3–60 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 indicate that while changing the C-2 methyl ester of cocaine to a C-2 phenyl ester increases dopamine-transporter selectivity, it dissociates its locomotor activity effects from its discriminative stimulus effects suggesting that the underlying mechanisms mediating these effects are not identical. |
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