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Ruffing DM, Domino EF. 
“First Dose Behavioral Tolerance to Phencyclidine on Food-Rewarded Bar Pressing Behavior in the Rat”. 
Psychopharmacology. 1980;69(1):1-4.
Abstract
The development of tolerance to the effects of a first dose of phenycyclidine (PC) was examined in operant-conditioned drug naive rats. Method The mean duration of cessation of conditioned responding (bar pressing for a food reward) was measured in groups of 4-8 adult male Holtzman rats after administration of PC (Sernylan, Biocoutic Laboratories) in single doses of 1, 1.8, 2.4 and 3.2 mg/kg, i.p. Dose-response curves were plotted for injections given at weekly intervals for 4 wk. The effects of PC (1 and 1.8 mg/kg, i.p.) N,N-dimethyltryptamine (DMT, Sigma) (3.2 and 10 mg/kg, i.p.) and LSD (Delysid 0.1 mg/kg, i.p.) on bar pressing behavior were studied, PC in first doses of 1-3.2 mg/kg disrupted bar pressing behavior in a dose-related manner. PC also produced gross behavioral reactions, e.g. ataxia, motor hyperactivity, repetitive body movements. The prolonged suppression of fixed ratio schedule behavior was exclusive for the first dose and no return in drug sensitivity was noted following a 4-wk drug-free interval. In animals receiving the first dose of PC in their home cages and subsequently receiving weekly doses in the operant chamber the duration of response disruption was increased with the second dose and was reduced following the third dose. Tolerance at the administration of the first dose was not observed with DMT and LSD. PC had nonspecific toxic effects in some animals.
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