Attenuation of the amphetamine discriminative cue in rats with the atypical antipsychotic olanzapine

Sixteen male Sprague–Dawley rats were trained to discriminate between saline and amphetamine injections (1.0 mg/kg ip) using a standard two-lever (FR10) drug discrimination paradigm. A baseline dose–effect curve was generated for amphetamine administration alone, using doses both above and below the training dose (0.0–2.2 mg/kg ip). Once completed, a single dose of olanzapine (OLZ; 1.5 mg/kg sc) was tested for its ability to attenuate the amphetamine cue. OLZ pretreatment (60 min) successfully interfered with an animal's ability to discriminate amphetamine injections across various doses. The percentage of correct responding on the amphetamine lever and rate of responding were both significantly decreased across some but not all of the amphetamine doses. Therefore, we believe that this preliminary investigation has successfully shown that an OLZ dose of 1.5 mg/kg sc at 60 min can interfere with an animal's ability to detect some subjective cue(s) associated with amphetamine administration.