Serotonin depletion decreases serotonin transporter mRNA levels in rat brain.
In order to study the impact of serotonin depletion on gene expression of the serotonin transporter (5-HTt) we measured 5-HTt mRNA levels by Northern blot in rats treated with p-chlorophenylalanine methyl ester (PCPA) for 10 days. Six rats received PCPA i.p. only, and another 6 rats receiving 0.9% NaCl served as controls. An additional group of 6 rats received both PCPA i.p. and imipramine, 5 mg/kg/day by osmotic minipumps. 5-HTt mRNA levels decreased to 81.1% (P = 0.05) and 76.0% (P = 0.05) of the control level for PCPA treated animals without and with concomitant imipramine treatment, respectively. The average level of the PCPA treated groups was 78.6% (P = 0.03). The isolated effect of 21 days of imipramine treatment was a 5-HTt mRNA level of 89.4%, which was not significantly different from the control level. In conclusion, 5-HTt gene expression is suppressed in the serotonin depleted state. A decreased synaptic reuptake of 5-HT may be interpreted as a compensatory mechanism aiming at preserving adequate synaptic 5-HT levels in a generally deficient state.
Linnet
K
K
Institute for Basic Research in Psychiatry, Psychiatric University Hospital, Risskov, Denmark.
Koed
K
K
Wiborg
O
O
Gregersen
N
N
D000818:Animals; D015152:Blotting, Northern; D002352:Carrier Proteins / Q000235:genetics*; D010134:Fenclonine / Q000031:analogs & derivatives / Q000494:pharmacology; D015870:Gene Expression; D007099:Imipramine / Q000494:pharmacology; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics*; D026901:Membrane Transport Proteins; D008636:Mesencephalon / Q000378:metabolism*; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger / Q000378:metabolism; D011903:Raphe Nuclei / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D012016:Reference Values; D012701:Serotonin / Q000172:deficiency*; D050486:Serotonin Plasma Membrane Transport Proteins; D013997:Time Factors
D002352:Carrier Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D050486:Serotonin Plasma Membrane Transport Proteins; C493232:Slc6a4 protein, rat; C020261:4-chlorophenylalanine methyl ester; D012701:Serotonin; D007099:Imipramine; D010134:Fenclonine