BIOGENIC AMINES AND NARCOTIC EFFECTS. I. MODIFICATION OF MORPHINE-INDUCED ANALGESIA AND MOTOR ACTIVITY AFTER ALTERATION OF CEREBRAL AMINE LEVELS

¹ Department of Pharmacology, Vanderbilt University School of Medicine and Tennessee Neuropsychiatric Institute, Nashville, Tennessee

The effect of modification of biogenic amine levels on morphine analgesia and motor activity was studied in the rat. Depletion of brain serotonin by p-chlorophenylalanine (300 mg/kg) or by lesioning of the raphe nuclei clearly did not antagonize morphine analgesia as measured by the hot-plate or tail-flick test. -Methyltryosine (78 mg/kg) produced a slight potentiation and prolongation of morphine analgesia. Reserpine (5 mg/kg, 24 hours) did not antagonize but instead appeared to produce a slight prolongation of morphine analgesia. However, alterations of amine levels produced rather selective modifications of the hyper- or hypoactivity induced by morphine. Morphine (4 mg/kg) produced an initial excitation lasting two hours followed by a return to normal motor activity. A dose of 16 mg/kg of morphine, however, produced an initial two-hour period of hypoactivity followed by a two-hour period of hyperactivity. p-Chlorophenylalanine pretreatment did not alter the hyperactivity observed after 4 mg/kg of morphine. However, p-chlorophenylalanine pretreatment and lesions in the raphe nuclei not only antagonized but reversed the hypoactivity caused by the higher dose of morphine. -Methyltyrosine antagonized the immediate and delayed increases in activity produced by 4 and 16 mg/kg of morphine respectively. Moreover, -methyltyrosine antagonized the hyperactivity observed after chronic (16 mg/kg t.i.d., 5-7 days) morphine administration. Reserpine antagonized both the hypoactivity and the hyperactivity. These data suggest that the motor activity observed after various morphine treatments in rats is dependent, in part, upon a balance between a catecholaminergic system which acts to increase motor activity and a serotonergic system which acts to decrease motor activity. The effects of morphine on these two systems appear to be both dose- and time-dependent.