Effects of morphine on dopamine metabolism in rat striatum and limbic structures in relation to the activity of dopaminergic neurones.

Administration of morphine results in efflux of dopamine provided that the nerve impulse flow of the dopaminergic neurones is impaired. In the present study we investigated whether the morphine-induced increase in dopamine metabolite levels is related to impulse flow in a similar way. Pretreatment with gamma-butyrolactone to impair nerve impulse flow, abolished the effect of morphine on the concentrations of dihydroxyphenylacetic acid and homovanillic acid. Pretreatment with apomorphine had a similar effect, as well as combined pretreatment with gamma-butyrolactone and apomorphine. Since gamma-butyrolactone and apomorphine both reduce nerve impulse flow, but gamma-butyrolactone increases while apomorphine decreases dopamine biosynthesis, it would appear that the antagonism of morphine-induced increases in dopamine metabolites is due to the common property of impulse flow reduction. It was also shown, however, that pretreatment with alpha-methyl-paratyrosine, which inhibits dopamine biosynthesis, resulted in antagonism of morphine's effect on dopamine metabolite levels. It is concluded, therefore, that morphine-induced dopamine efflux is observed under conditions when no effect on dopamine metabolism is observed, and vice versa. Three effects of morphine on dopaminergic neurones can be distinguished: an increase in impulse flow in nigrostriatal dopaminergic neurones, increased dopamine biosynthesis and catabolism, and efflux of dopamine. The first effect probably is effected in the cell body areas, while the latter two effects may be produced at the level of the nerve terminals.(ABSTRACT TRUNCATED AT 250 WORDS)