Dopamine receptor pruning during the peripubertal period is not attenuated by NMDA receptor antagonism in rat.
D(1) and D(2) receptors are overproduced and pruned in the mammalian striatum during the periadolescent period. The mechanism that underlies this process in striatum is unknown. However, previous research has shown that the activity-dependent pruning of dendrites and synapses in somatosensory cortex and the visual fields is mediated by glutamatergic actions via N-methyl-D- aspartate (NMDA) receptor and is prevented by pretreatment with the NMDA antagonist MK-801. In order to test the hypothesis that the pruning of dopamine D(1) and D(2) receptors that occurs in the striatum after puberty (which occurs at approximately 40 days of age; P40), male and female rats were treated with saline vehicle or MK-801 (0.3 mg/kg) for 20 or 40 days and sacrificed immediately after the 20 day treatment (P60), 40 day treatment (P80), or 40 day treatment with 40 day recovery (P120). Analyses of the data reveal that none of these three treatment regimens altered striatal D(1) or D(2) receptor density in males or females relative to vehicle controls. At P60, MK-801 treatment failed to alter either D(1) (F1,16=0.06, P>0.5) or D(2) receptors (F1,16=0.39, P>0.5) for either sex. Similarly, MK-801 treatment did not affect D(1) or D(2) receptors at P80 (P>0.3) or at P120 (P>0.7). These data suggest that the normal 40% reduction in striatal dopamine receptor density that occurs between puberty and adulthood is not dependent on post-pubertal glutamatergic transmission through NMDA receptors.
Teicher
M H
MH
Developmental Psychopharmacology Laboratory, McLean Hospital, 115 Mill Street, Belmont, MA 02478, USA.
Krenzel
E
E
Thompson
A P
AP
Andersen
S L
SL
D000375:Aging / Q000378:metabolism*; D000818:Animals; D001345:Autoradiography; D003342:Corpus Striatum / Q000378:metabolism*; D016291:Dizocilpine Maleate / Q000494:pharmacology; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D011869:Radioligand Assay; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D012737:Sex Factors
D017447:Receptors, Dopamine D1; D016194:Receptors, N-Methyl-D-Aspartate; D016291:Dizocilpine Maleate