In some experiments, the selective 5-HT3 antagonist ondansetron (Sigma Chemical) was administered. For systemic administration, ondansetron was injected s.c. in 100 μl volumes of 0.9% NaCl to some groups of mice. The drug was either given at a dose of 1 mg/kg along with each dose of morphine during the chronic dosing paradigm, or given once over a range of doses 30 min before dependence or nociceptive testing. For intracerebroventricular (i.c.v.) administration, mice were briefly anesthetized with inhaled isoflurane. A 30-gauge half-inch needle was used to pierce the skull and enter the ventricles using an approach described previously [18]. Once inserted, 5 μl of injectate was slowly administered using a microsyringe, and the animals were used within 20 min after the injection.
