Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0220723 (PCA)
 4,687 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This study examined the effects of parachloroamphetamine on neonatal forebrain serotonergic (5-HT) innervation. Rat pups were treated with PCA on P3 and P4. Significant reductions in 5-HT content were observed in the hippocampal formation, frontal cortex and entorhinal cortex on P5 and P7. By P14, neocortical 5-HT had returned to normal levels while hippocampal 5-HT values remained less than control. Hippocampal 5-HT content reached normal range by P21. High affinity 5-HT uptake in hippocampal synaptosomal preparations was similarly reduced on P5 and P7 suggesting that 5-HT terminals were being lesioned by PCA. 5-HT uptake recovered significantly by P14 perhaps reflecting the extraordinary plasticity of the 5-HT projections in the neonate. However, in contrast to the complete restoration of hippocampal 5-HT content, 5-HT uptake values remained significantly less than control. No change in 5-HT content was observed in either the hypothalamus or midbrain raphe at any age studied. Thus, the rapid onset of effects, regional selectivity and transient reduction of 5-HT levels recommend the use of PCA in studies of the role of 5-HT in hippocampal development.
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PMID:Transient reduction in hippocampal serotonergic innervation after neonatal parachloroamphetamine treatment. 769 67

We have previously reported that neonatal (P3) serotonin (5-HT) depletion results in a significant decrease in the number of dendritic spines per 50 microns of dendritic length on dentate granule cells. This effect is specific and permanent. Neither total dendritic length nor the number of dendritic segments is affected by 5-HT depletion. The area dentata contains a dense 5-HT1a receptor population that is present in the at birth. Therefore, 5-HT1a receptors represented a likely candidate for the mediation of the effects of 5-HT on developing granule cells. The present study used the drugs buspirone and NAN-190, which have been shown to be an agonist and antagonist respectively at postsynaptic 5-HT1a receptors in vivo, to test the idea that neurotrophic actions of 5-HT result from 5-HT1a receptor stimulation. Following 5-HT depletion with PCA, pups received daily injections of buspirone (1.0 mg/kg) from P5 to P14. Granule cell morphology was then studied using intracellular filling with Neurobiotin on P14, P21 and P60. Buspirone treatment prevented the loss of dendritic spines previously shown to follow 5-HT depletion with PCA. No other morphological parameters were significantly changed by buspirone treatment. Naive pups received daily injections of NAN-190 from P3 to P14. One group received 1.0 mg/kg while a second group received 3.5 mg/kg. Both doses of NAN-190 resulted in dendritic spine loss comparable to that obtained with neonatal PCA treatment. This loss was permanent suggesting that the first two postnatal weeks may represent a critical period for the action of 5-HT on developing granule cells. Significant, dose-dependent changes in total dendritic length and number of dendritic segments reminiscent of the effects of norepinephrine depletion were also observed in NAN-190-treated rats. We suspect that this change is the result of the action NAN-190 at alpha receptors and is therefore distinct from the specific effect of 5-HT on the number of dendritic spines. The NAN-190 experiment also shows that the loss of dendritic spines is a function of decreased stimulation of 5-HT1a receptors and not the loss of 5-HT terminal membrane.
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PMID:5-HT1a receptors mediate the neurotrophic effect of serotonin on developing dentate granule cells. 905 Dec 59