Drug pretreatment effects in drug induced taste aversions: effects of dose and duration of pretreatment.

The effectiveness of a dose of 3.0 mg/kg methamphetamine in inducing a conditioned taste aversion to saccharin was found to be reduced by chronic pretreatment with the same dose of the drug. The degree of attenuation of the aversive properties of the drug was found to be directly proportional to the duration of pretreatment, a pretreatment regime of 9 or more daily injections completely abolishing the aversive properties of the drug. However, such a regime was only slightly effective in attenuating the aversive properties of a higher dose of methamphetamine (10 mg/kg) and failed to attenuate the aversive properties of a number of other drugs (p-chloramphetamine at 5.0 mg/kg, fenfluramine at 5.0 mg/kg and morphine at 20 mg/kg). Interpretations of these data are considered and it is suggested that the most parsimonious explanation of the effectiveness of chronic drug pretreatment in attenuating the aversive properties of a drug is that the effect is due to the development of tolerance to the drug administered.