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 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 (> or = 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.
Cook
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CD
Department of Psychology, University of North Carolina, Chapel Hill 27599-3270, USA.
Carroll
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FI
Beardsley
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PM
D000818:Animals; D002352:Carrier Proteins / Q000187:drug effects; D000697:Central Nervous System Stimulants / Q000737:chemistry / Q000494:pharmacology*; D003042:Cocaine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology*; D003216:Conditioning, Operant / Q000187:drug effects; D003463:Cues; D004193:Discrimination Learning / Q000187:drug effects / Q000502:physiology*; D050483:Dopamine Plasma Membrane Transport Proteins; D018765:Dopamine Uptake Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005795:Generalization, Stimulus; D008297:Male; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D051379:Mice; D008813:Mice, Inbred ICR; D009043:Motor Activity / Q000187:drug effects*; D009419:Nerve Tissue Proteins; D051381:Rats; D017207:Rats, Sprague-Dawley; D013329:Structure-Activity Relationship
D002352:Carrier Proteins; D000697:Central Nervous System Stimulants; D050483:Dopamine Plasma Membrane Transport Proteins; D018765:Dopamine Uptake Inhibitors; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D003042:Cocaine