Dose-response relationship between acute and chronic heroin doses and jumping frequency. ACUTE (top figure): Mice received a single injection of various heroin doses followed 2 h later by naloxone. CHRONIC (bottom figure): Mice were injected t.i.d. for three days with escalating heroin doses (5, 10, and 20 or 10, 20, and 40 mg/kg on treatment Days 1, 2, and 3, respectively) and a final single heroin dose (40 mg/kg) on Day 4. Withdrawal was precipitated by injecting naloxone (50 mg/kg). Heroin control mice in both treatment paradigms were injected with saline instead of naloxone after injecting the heroin dose eliciting the greatest jumping frequency. Significant differences from control group (**P <0.01) and all other non-control groups (+) are indicated.