Development of dopamine autoreceptors in the postnatal rat brain.
The behavioural and biochemical effects of racemic 3-PPP (3-[3-hydroxyphenyl]-N-n-propyl-piperidine) and its enantiomers was studied in developing rats, aged 1-28 days. All three compounds exhibit dopamine (DA) autoreceptor-stimulating properties. Moreover, the (+)-enantiomer displays agonist and the (-)-enantiomer antagonist actions, respectively, on the postsynaptic DA receptor. This means that the racemate has a DA autoreceptor stimulatory action with slight or no effects on the postsynaptic receptor. Locomotor experiments demonstrated that (+/-)-3-PPP inhibited spontaneous locomotor activity dosedependently in the 28 days old rats. No effects were seen in the age groups 14 days and younger. While the racemate and the (-)-enantiomer inhibited spontaneous locomotor activity in 28 days old rats, the (+)-enantiomer had no effects compared to saline. Interestingly, the (+)-enantiomer increased locomotor activity in the 4 days old rats, while the (-)-enantiomer and the racemate did not induce any effects. In the biochemical experiments, after blockade of DA neurotransmission with gamma-butyrolactone (GBL), (+/-)-3-PPP inhibited the increase in tyrosine hydroxylase activity (DOPA accumulation after NSD 1015) after GBL in the DA rich striatum region of the 28 days but not of the 4 days old rats. From these experiments it may be concluded that functional postsynaptic but not presynaptic DA receptors exist in the brain of 4 days old rats. Presynaptic DA receptors do not seem to be functionally mature until 28 days postnatally in the rat, i.e. during adolescent age.
D015102:3,4-Dihydroxyphenylacetic Acid / Q000032:analysis; D000367:Age Factors; D000818:Animals; D001921:Brain / Q000254:growth & development*; D001923:Brain Chemistry / Q000187:drug effects; D004295:Dihydroxyphenylalanine / Q000032:analysis; D009043:Motor Activity / Q000187:drug effects; D009638:Norepinephrine / Q000032:analysis; D010880:Piperidines / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000502:physiology*; D013237:Stereoisomerism
D010880:Piperidines; D011954:Receptors, Dopamine; D015102:3,4-Dihydroxyphenylacetic Acid; D004295:Dihydroxyphenylalanine; C026539:preclamol; D009638:Norepinephrine