Opposing changes in serotonin and norepinephrine transporter mRNA levels after serotonin depletion.
We and others have earlier shown that severe serotonin depletion leads to a compensatory down-regulation in the expression of the serotonin transporter (5HTT) gene. We have now investigated the expression of both the 5HTT and the norepinephrine transporter (NET) gene to assess the possible interaction between the noradrenergic and the serotonergic neurotransmitter systems. Acute severe serotonin depletion induced by p-chlorophenylalanine (PCPA) treatment leads to enhanced NET(Long) mRNA levels and reduced 5HTT mRNA level. This change in transporter mRNA expression was paralleled by a non-significant change in protein expression. Chronic severe serotonin depletion combined with treatment with the antidepressant imipramine leads to enhanced NET(Long) mRNA levels. Acute treatment with the monoamine oxidase A inhibitor clorgyline, acute moderate NE reduction (alpha-methyl-p-tyrosine treatment) or less severe depletion for 3 weeks have no effect on the gene expression of the transporters. Taken together, the present data demonstrate that the NET gene expression is enhanced in case of severe serotonin depletion.
Koed
K
K
Institute for Basic Research in Psychiatry, Department of Biological Psychiatry, Psychiatric Hospital in Aarhus, The Aarhus University Hospital, Skovagervej 2, DK-8240, Risskov, Denmark. kak@psykiatri.aaa.dk
Linnet
K
K
D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D004032:Diet; D004347:Drug Interactions; D010134:Fenclonine / Q000494:pharmacology; D007099:Imipramine / Q000494:pharmacology; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D009638:Norepinephrine / Q000172:deficiency / Q000378:metabolism*; D050484:Norepinephrine Plasma Membrane Transport Proteins; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000172:deficiency / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000494:pharmacology; D050486:Serotonin Plasma Membrane Transport Proteins; D027981:Symporters; D014364:Tryptophan / Q000172:deficiency / Q000378:metabolism
D018759:Adrenergic Uptake Inhibitors; D002352:Carrier Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D050484:Norepinephrine Plasma Membrane Transport Proteins; D012333:RNA, Messenger; D012702:Serotonin Antagonists; D050486:Serotonin Plasma Membrane Transport Proteins; C493226:Slc6a2 protein, rat; C493232:Slc6a4 protein, rat; D027981:Symporters; D012701:Serotonin; D014364:Tryptophan; D007099:Imipramine; D010134:Fenclonine; D009638:Norepinephrine