TY - JOUR
T1 - Substitution and cross-tolerance profiles of anorectic drugs in rats trained to detect the discriminative stimulus properties of cocaine
AU - Wood, Douglas M.
AU - Emmett-Oglesby, Michael W.
PY - 1988/7
Y1 - 1988/7
N2 - Rats were trained to discriminate cocaine, 10.0 mg/kg, using a two-lever operant procedure. Dose-effect data were determined for the substitution of cocaine, diethylpropion, methylphenidate, phenmetrazine, phentermine, and fenfluramine for the cocaine stimulus. All of these drugs, except fenfluramine, substituted fully for the cocaine stimulus. Subsequently, training was halted and cocaine, 20 mg/kg/8 h, was administered for 9 days, and dose-effect data were redetermined for all of these drugs on days 7-9 of chronic administration. Chronic administration of cocaine produced tolerance to the stimulus properties of cocaine, and cross-tolerance to the stimulus properties of methylphenidate, phenmetrazine, and phentermine, such that doses approximately two-fold higher than those used acutely were necessary to reproduce the original effect; the potency for the substitution of diethylpropion for the cocaine stimulus was decreased greater than four-fold; and fenfluramine still failed to substitute for the cocaine stimulus. These data suggest that 1) a common mechanism may mediate tolerance to the discriminative stimulus properties of cocaine, methylphenidate, phenmetrazine, and phentermine, and 2) tolerance in the drug discrimination procedure may have potential for establishing a comprehensive evaluation of dependence liability of CNS stimulants.
AB - Rats were trained to discriminate cocaine, 10.0 mg/kg, using a two-lever operant procedure. Dose-effect data were determined for the substitution of cocaine, diethylpropion, methylphenidate, phenmetrazine, phentermine, and fenfluramine for the cocaine stimulus. All of these drugs, except fenfluramine, substituted fully for the cocaine stimulus. Subsequently, training was halted and cocaine, 20 mg/kg/8 h, was administered for 9 days, and dose-effect data were redetermined for all of these drugs on days 7-9 of chronic administration. Chronic administration of cocaine produced tolerance to the stimulus properties of cocaine, and cross-tolerance to the stimulus properties of methylphenidate, phenmetrazine, and phentermine, such that doses approximately two-fold higher than those used acutely were necessary to reproduce the original effect; the potency for the substitution of diethylpropion for the cocaine stimulus was decreased greater than four-fold; and fenfluramine still failed to substitute for the cocaine stimulus. These data suggest that 1) a common mechanism may mediate tolerance to the discriminative stimulus properties of cocaine, methylphenidate, phenmetrazine, and phentermine, and 2) tolerance in the drug discrimination procedure may have potential for establishing a comprehensive evaluation of dependence liability of CNS stimulants.
KW - Amphetamine
KW - CNS stimulants
KW - Cocaine
KW - Drug discrimination
KW - Rat
KW - Tolerance
UR - http://www.scopus.com/inward/record.url?scp=0023945024&partnerID=8YFLogxK
U2 - 10.1007/BF00181948
DO - 10.1007/BF00181948
M3 - Article
C2 - 3137623
AN - SCOPUS:0023945024
SN - 0033-3158
VL - 95
SP - 364
EP - 368
JO - Psychopharmacologia
JF - Psychopharmacologia
IS - 3
ER -