@article {BUXBAUM317, author = {D. M. BUXBAUM and G. G. YARBROUGH and M. E. CARTER}, title = {BIOGENIC AMINES AND NARCOTIC EFFECTS. I. MODIFICATION OF MORPHINE-INDUCED ANALGESIA AND MOTOR ACTIVITY AFTER ALTERATION OF CEREBRAL AMINE LEVELS}, volume = {185}, number = {2}, pages = {317--327}, year = {1973}, publisher = {American Society for Pharmacology and Experimental Therapeutics}, abstract = {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. {\textcopyright} 1973 by The Williams \& Wilkins Co.}, issn = {0022-3565}, URL = {https://jpet.aspetjournals.org/content/185/2/317}, eprint = {https://jpet.aspetjournals.org/content/185/2/317.full.pdf}, journal = {Journal of Pharmacology and Experimental Therapeutics} }