Synthesis rate of dopamine: difference between corpus striatum and limbic system as a possible explanation of variations in reactions to drugs.
The synthesis rate of dopamine and noradrenaline in different parts of the rat brain was estimated by measuring the accumulation of DOPA following decarboxylase inhibition. Although the synthesis of dopamine was enhanced in all regions by haloperidol and gammabutyrolactone, it was increased to almost 400% of the control in the corpus striatum but to only somewhat more than 200% in the olfactory tubercle and some other limbic regions. The dopamine autoreceptor agonist B-HT 920 was more potent and effective in lowering the synthesis of dopamine in the limbic regions than in the corpus striatum. These differences between the extrastriatal and striatal brain areas in the pharmacological responses might be explained by a 50% higher norma synthesis rate constant of the dopamine in the limbic system than in the corpus striatum. The lower dopamine synthesis rate in the latter region may be due to a negative neuronal feedback from the corpus striatum to the substantia nigra. Functional studies support this proposal. Indeed, B-HT 920 was less effective than haloperidol in changing the direction of head turning of rats with a diencephalic hemisection at doses equieffective in reducing the motor activity. The findings indicate that B-HT 920 is relatively more potent than haloperidol in inhibiting the dopamine neurotransmission in the limbic system than in the corpus striatum.
D000818:Animals; D001381:Azepines / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects; D001923:Brain Chemistry / Q000187:drug effects; D003342:Corpus Striatum / Q000378:metabolism*; D004298:Dopamine / Q000096:biosynthesis*; D005246:Feedback; D006220:Haloperidol / Q000494:pharmacology; D007700:Kinetics; D008032:Limbic System / Q000378:metabolism*; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009638:Norepinephrine / Q000096:biosynthesis; D051381:Rats; D011919:Rats, Inbred Strains
D001381:Azepines; C024763:talipexole; D006220:Haloperidol; D004298:Dopamine; D009638:Norepinephrine