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The effect of the acute administration of morphine (60 mg/kg) on the metabolism of dopamine (DA) and tyrosine in the rat striatum were investigated using in vivo and in vitro methods. 30 min after morphine injection, the initial accumulation of 3H-DA in tissues seen after the i.v. injection of L-3,5-H-tyrosine was enhanced as well as the accumulation of 3HH2O and 3H-DA in tissues and medium of striatal slices incubated with the 3H precursor. These results and the estimation of the conversion index of tyrosine into DA (3H-DA/tyrosine specific activity) indicated that morphine stimulated DA synthesis. This effect was not seen 2 hr later. The enhanced DA synthesis was associated with a parallel increase in the release of newly synthesized 3H-DA as indicated by the greater accumulation of 3H-DA in incubating medium of slices of morphine-pretreated rats. Therefore the increased endogenous levels of DA seen after morphine are related to the increased synthesis of the transmitter. Apart from its effect on dopaminergic neuron activity, morphine also induced marked changes in tyrosine metabolism, particularly at 2 or 2.5 hr after its injection. Tyrosine levels in plasma and in striatum were about 160% of the control levels at this time: these changes in the size of the precursor pool may explain the enhanced accumulation of 3H-tyrosine seen in plasma and striatum 10 min after the 3H-amino acid injection. Marked changes in endogenous levels of DA and tyrosine occurred in the striatum of control animals from 9.00 to 12.00 am. Acute treatment with morphine significantly affected these diurnal variations.

Dopamine levels in the neostriatum of the rat were estimated at various times after pargyline (75 mg/kg), pheniprazine (4 mg/kg) and tranylcypromine (20 mg/kg) intraperitoneal injections. Depending on the inhibitor used, the amine levels reached 135 to 150% of control values within 10 min. During the 20 min which followed this rapid linear rise, DA levels increased in tissues at a much slower rate. As indicated by the estimation of MAO activity using14C-tyramine or kynuramine as substrates, the three drugs induced a complete inhibition of the enzyme activity within 5 min. A similar effect was seen after pheniprazine and tranylcypromine with14C-dopamine as substrate, but the maximal inhibition never exceeded 80% after pargyline treatment. As revealed by the “in vivo” 3 min initial accumulation of3H-H2O seen at the end of a local infusion of L. 3. 5-3H-tyrosine, the rate of the first step of DA synthesis was unchanged 5 min after pargyline treatment but significantly reduced 10 min after the drug injection. This explains the sudden interruption in the rise of DA levels observed shortly after the MAO inhibitors injection. DA synthesis rate was calculated from the initial (5 min) rate of DA accumulation and was found to be 148 to 190 nmole/g/hr depending on the inhibitor used.

Monoamine oxidase and aldehyde dehydrogenase activity were significantly reduced in the striatum of rats 8 days after lesion of the nigrostriatal nerve pathway caused by 6-hydroxydopamine. Evidence is presented for the existence of an intraneuronal 'dopamine monoamine oxidase' and intraneuronal aldehyde dehydrogenase. Dopamine concentrations were reduced to 10% of their control values.