Clozapine was provided as a generous gift to J.H.P. from Novartis (Hanover, NJ, USA). Olanzapine was provided as a generous gift to J.H.P. from Eli Lilly (Indianapolis, IN, USA). Clozapine, olanzapine, and risperidone were supplied to D.W. by the National Institute of Mental Health’s Chemical Synthesis and Drug Supply Program. Haloperidol, prazosin, propranolol, and ritanserin were purchased from Sigma-Aldrich (St. Louis, MO, USA). J.H.P. and M.S.F. obtained CNO from the Rapid Access to Investigative Drug Program funded by the National Institute of Neurological Disorders and Stroke. D.W. obtained CNO from the National Institute on Drug Abuse Drug Supply Program.
Clozapine, olanzapine, risperidone, haloperidol, prazosin, propranolol, and ritanserin were each dissolved in distilled water with 2–3 drops of lactic acid and pH-adjusted to 6.0–7.0 with NaOH. For mouse drug discrimination studies, CNO was also dissolved in this vehicle. For rat drug discrimination studies and for mouse and rat pharmacokinetic analyses, CNO was dissolved in bacteriostatic saline containing v/v 2.5–5.0% dimethyl sulfoxide (Sigma-Aldrich) and 10% Cremophor EL (Sigma-Aldrich).
For mouse drug discrimination studies, all drugs were administered s.c. at a volume of 10 ml/kg, 30 min prior to session onset. For rat drug discrimination studies, all drugs were administered i.p. at a volume of 1 ml/kg. Clozapine was administered 60 min prior to session onset, while olanzapine, risperidone, prazosin, and propranolol were administered 30 min prior to session onset. CNO was tested at both 30 and 60 min pretreatment times. All drug doses are expressed as the salt weight.
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