Tolerance and sensitization to the heart-rate effects of morphine

The effect of daily exposure to one of several doses of morphine (0, 2.0, 4.0 and 8.0 mg/kg IV) on heart rate was assessed in restrained (R) and unrestrained (U) rats. Initially, morphine produced a biphasic heart-rate response; bradycardia followed by tachycardia. Tolerance to the bradycardic effect was established in the 4 and 8 mg/kg R groups and in the 2 and 4 mg/kg U groups. Sensitization developed to the tachycardic effect in the 2 and 4 mg/kg U groups but not in the 8 mg/kg U group or any of the R groups. After several exposures to morphine, mean preinfusion heart rate increased in the 4 and 8 mg/kg dose groups but not in the 0 and 2 mg/kg dose groups. These results are generally consistent with the other data suggesting that tolerance develops only to the depressant effects of morphine, and either no change or sensitization develops to its stimulant effects. The development of higher preinfusion heart rates in the higher dose groups may represent a learned anticipatory response.