6-OHDA lesion to the dorsal noradrenergic bundle alters morphine-induced locomotor activity and catalepsy

Rats show an initial depression in locomotor activity in response to doses of morphine greater than 5 mg/kg during the first hour after injection which is followed by a prolonged hyperactive phase. The effect of bilateral 6-hydroxydopamine (6-OHDA) lesions to the dorsal noradrenergic bundle on this biphasic action of morphine was studied. These lesions were found to significantly potentiate the locomotor depressant effects of morphine at 10.0 and 20.0 mg/kg while leaving the subsequent stimulant action of morphine unchanged. The cataleptic action of morphine at 20.0 mg/kg as measured in a separate test was also potentiated. These lesions were found to deplete hippocampal and cortical noradrenaline (NA) to 3% and hypothalamic NA to 32% of control values and also to cause significant increases in cerebellar and spinal NA. These data suggest a role for NA in the depressant effects of morphine but not in its subsequent stimulant actions which appear to be mediated by other neurochemical systems.