RT Journal Article
SR Electronic
T1 BIOGENIC AMINES AND NARCOTIC EFFECTS. I. MODIFICATION OF MORPHINE-INDUCED ANALGESIA AND MOTOR ACTIVITY AFTER ALTERATION OF CEREBRAL AMINE LEVELS
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 317
OP 327
VO 185
IS 2
A1 D. M. BUXBAUM
A1 G. G. YARBROUGH
A1 M. E. CARTER
YR 1973
UL http://jpet.aspetjournals.org/content/185/2/317.abstract
AB 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. α-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. α-Methyltyrosine antagonized the immediate and delayed increases in activity produced by 4 and 16 mg/kg of morphine respectively. Moreover, α-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. © 1973 by The Williams & Wilkins Co.