Time-response study of naloxone precipitated withdrawal from acute and chronic heroin treatment. ACUTE (top figure): mice were injected with a single heroin dose (50 mg/kg). CHRONIC (bottom figure): mice were injected t.i.d. for three days with escalating heroin doses (10, 20, and 40 mg/kg on treatment Days 1, 2, and 3, respectively) and a final 40 mg/kg heroin dose on Day 4. Withdrawal was precipitated by injecting naloxone (50 mg/kg) at various intervals after heroin treatment was completed. Control mice were subject to the identical acute or chronic heroin treatment protocols but received saline injections in place of either heroin or naloxone and tested at the heroin-naloxone interval yielding maximal frequencies. Significant differences from control values (* P <0.05; ** P <0.01) are indicated.