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

Arc (activity regulated, cytoskeleton associated protein) is an effector immediate early gene that is selectively localized in the neuronal dendrites. Elevation of brain 5-HT by the combined administration of the monoamine oxidase inhibitor, tranylcypromine (TCP, 5 mg/kg, i.p.), and the 5-HT precursor L-tryptophan (L-TP, 100 mg/kg, i.p.), increased Arc mRNA abundance in the cingulate, orbital, frontal and parietal cortices as well as in the striatum but a reduction was observed in the CA1 region of the hippocampus. The 5-HT releasing agent p-chloroamphetamine (PCA, 5 mg/kg, s.c.) also increased Arc mRNA in the cortical and striatal areas. Depleting brain 5-HT with the tryptophan hydroxylase inhibitor, p-chlorophenylalanine (pCPA, 300 mg/kg, i.p. for two days), on the other hand, significantly attenuated the increase in Arc mRNA induced by tranylcypromine and L-tryptophan (TCP/L-TP). Pretreatment with the 5-HT2 receptor antagonist ketanserin (2 mg/kg, i.p.) significantly attenuated the effect of TCP/L-TP in the cortex but only partially in striatum and did not affect the reduction in the CA1 region. The 5-HT2 agonist DOI (0.2, 1 and 2 mg/kg, i.p.) dose-dependently increased Arc mRNA abundance in cortical areas with a pattern similar to that of TCP/L-TP and PCA. DOI, however, had much weaker effects on Arc mRNA in the striatum and did not have any significant effect in the CA1, CA3 and the dentate gyms (DG) of the hippocampus. Pretreatment with ketanserin completely blocked the effect of DOI on Arc expression. These data suggest that Arc mRNA expression can be induced in the cortex by increases in extracellular 5-HT and that 5-HT2 receptors play a major part in mediating such effects. Additional 5-HT receptors as well as other neurotransmitters may also be involved, particularly in the striatum and in CA1 subfield of the hippocampus. Overall, our data suggest that expression of Arc mRNA is highly responsive to changes in brain 5-HT functions, and may provide a sensitive marker of postsynaptic 5-HT2(2A and 2C) receptor functions.
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PMID:Serotonergic regulation of mRNA expression of Arc, an immediate early gene selectively localized at neuronal dendrites. 1069 12

Stressful experiences and genetic predisposition have both independent and interactive contributions to the development of depression. The serotonergic system is involved in the development of depression, and administration of neurotoxins that specifically compromise its function leads to symptoms of affective disorders. In order to find out which brain regions are most affected by stress, partial serotonergic denervation and their combination, chronic variable stress (CVS) was applied for 3 week. Serotonergic denervation was elicited by parachloroampetamine (PCA, 2mg/kg), and cytochrome oxidase histochemistry was used to characterize the long-term levels of neuronal oxidative energy metabolism. PCA pretreatment blocked the increase in oxidative activity in chronically stressed rats in medial preoptic area, cortical and medial amygdala. PCA raised oxidative activity compared to control animals in substantia nigra and ventrolateral division of laterodorsal thalamus. CVS reduced the oxidative activity induced by PCA in suprachiasmatic hypothalamus, anteroventral thalamus, hippocampal CA3 region and cortical amygdala. In the dorsal part of the anterior olfactory nucleus chronic stress blocked the decrease in oxidative activity evoked by PCA. Conclusively, partial serotonergic denervation with PCA and chronic variable stress both had independent effects on long-term energy metabolism in several rat brain structures, tending to increase it. However, partial serotonergic denervation by parachloroampetamine and chronic variable stress had in many brain regions an interactive effect on energy metabolism, each factor reducing the effect of the other, which could reflect the weakening of adaptive mechanisms.
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PMID:Changes in regional long-term oxidative metabolism induced by partial serotonergic denervation and chronic variable stress in rat brain. 1788 57