Behavioral tolerance and cross-tolerance to dl-cathinone and d-amphetamine in rats

Abstract

The effects of dl-cathinone (0.25-48 mg/Kg, i.p. and d-amphetamine (0.25-8.0 mg/kg, i.p.) on milk intake in rats were determined before, during and after a period of repeated daily administration of dl-cathinone. Experimental sessions consisted of 15-min access to a sweetened milk solution each day. 7 days a week. After the determination of the acute effects of dl-cathinone and d-amphetamine on milk intake, rats were injected daily with either 4.0 mg/kg of dl-cathinone 15 min before each session and saline 15 min after each session; or saline 15 min before each session and 4.0 mg/kg of dl-cathinone 15 min after each session. Milk intake returned toward base-line levels for animals receiving daily dl-cathinone before the session over a period of 16 sessions, and remained slightly decreased compared to animals that received postsession injections. Dose-response functions for dl-cathinone and d-amphetamine were then redetermined by substituting a test dose for the usual presession injection once every 4 to 5 days. In animals that were receiving presession dl-cathinone, both drugs had less effect, indicating the development of tolerance to dl-cathinone and cross tolerance to d-amphetamine. The development of tolerance to the suppression of milk drinking was contingent upon the relationship of the time of the daily injection to milk availability. Animals that were receiving dl-cathinone after the session did not develop tolerance but were more sensitive to the effects of both drugs on milk intake. Dose-response functions for both drugs determined after 10 drug free days were similar to the initial dose-response functions, indicating the transient nature of the tolerance and supersensitivity.