Antagonism of the acute electroencephalographic and behavioral effects of morphine in the rat by depletion of brain biogenic amines

Abstract

Adult female Sprague-Dawley rats were prepared with chronically implanted cortical and temporalis muscle electrodes for recording of the electroencephalogram (EEG) and the electromyogram (EMG). Morphine injections of 10 mg/kg given i.p. to saline-treated rats were followed almost immediately by the appearance of high voltage EEC slow bursts associated with stuporous behavior, which prevailed for 60–90 min. This phase was superseded by the prevalence of EEG and behavioral arousal over an additional period of 60–90 min, after which EEG and behavioral sleep appeared. Administration of a 10 mg/kg dose of morphine to rats pretreated with (±)-alpha-methyl-para-tyrosine(α-MPT) was followed by a slight but significant shortening of the period of EEG slow bursts and the behavioral stupor as well as by a reduction in the duration of the entire morphine effect. In contrast, rats pretreated with para-chlorophenylalanine ( p-CPA) responded to morphine by an almost immediate and continuous EEG and behavioral arousal, with only a few intervening episodes of behavioral stupor associated with EEG slow bursts. This effect of p-CPA was completely reversed by the administration of 5-hydroxytryptophan (5-HTP) prior to the morphine injection. Pretreatment of the rats with both p-CPA and α-MPT likewise resulted in an attenuation of the period of morphine-induced EEG and behavioral stupor concomitant with a prolongation of the period of behavioral arousal. The effects of this treatment, however, were less pronounced than those occurring after p-CPA alone. These results suggest that the relative amounts of all three monoamines norepinephrine, dopamine, and 5-hydroxytryptamine in the brain, rather than the absolute levels of any one amine, are important in the mediation of the central effects of morphine.