Self-administration of cocaine analogs by rats.
BACKGROUND
A novel scheme for the synthesis of cocaine analogs from vinylcarbenoid precursors has made available compounds that have a diverse range of affinities for the DA and 5-HT transporters. These compounds were used to explore the relationship between their biochemical properties and their reinforcing effects.


OBJECTIVE
The objective was to assess the reinforcing efficacy of selected cocaine analogs and compare the results with their selectivity in binding to DA and 5-HT transporters.


METHODS
Rats were prepared with chronically indwelling intravenous cannulae and trained to self-administer cocaine on a progressive ratio (PR) schedule. A range of doses of seven cocaine analogs were substituted for cocaine in separate groups of animals.


RESULTS
The results demonstrate a wide range of reinforcing efficacies and potencies among the seven selected drugs. Four tropane analogs (WF-11, WF-23, WF-24, WF-55) were found to support self-administration behavior on a PR schedule while three did not (WF-31, WF-54 and WF-60). The DA/5-HT selectivity ratio was found to be a better predictor of self-administration behavior than affinity at the DA transporter alone.


CONCLUSIONS
These data suggest that drugs with a higher affinity for the DA versus the 5-HT transporter are more likely to be self-administered.
Roberts
D C
DC
Department of Physiology and Pharmacology, Wake Forest University School of Medicine, Winston-Salem, NC 27157-1083, USA. dcsrobts@wfubmc.edu
Phelan
R
R
Hodges
L M
LM
Hodges
M M
MM
Bennett
B
B
Childers
S
S
Davies
H
H
D000818:Animals; D002352:Carrier Proteins / Q000187:drug effects*; D003042:Cocaine / Q000008:administration & dosage* / Q000031:analogs & derivatives*; D019970:Cocaine-Related Disorders / Q000209:etiology*; D018492:Dopamine Antagonists / Q000494:pharmacology*; D050483:Dopamine Plasma Membrane Transport Proteins; D008297:Male; D008562:Membrane Glycoproteins / Q000187:drug effects*; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D051381:Rats; D017208:Rats, Wistar; D012055:Reinforcement Schedule; D012646:Self Administration; D050486:Serotonin Plasma Membrane Transport Proteins; D014326:Tropanes / Q000008:administration & dosage
D002352:Carrier Proteins; D018492:Dopamine Antagonists; D050483:Dopamine Plasma Membrane Transport Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D050486:Serotonin Plasma Membrane Transport Proteins; C493232:Slc6a4 protein, rat; D014326:Tropanes; C114627:WF 11; D003042:Cocaine