Lack of effect of antidepressant drugs on the levels of mRNAs encoding serotonergic receptors, synthetic enzymes and 5HT transporter.
Serotonergic transmission is thought to be central to the aetiology of depression and the therapeutic actions of antidepressant drugs, and the latters' delayed effect has given rise to the hypothesis that an adaptive change may be involved, possibly at the level of gene expression. We have examined this hypothesis by treating rats over a time course of up to 32 days with either imipramine, mianserin, fluvoxamine, citalopram, amoxapine or saline and measuring the levels of mRNAs encoding the 5HT1A, 5HT1B, 5HT1C and 5HT2 receptors, the enzymes tryptophan hydroxylase and aromatic amino acid decarboxylase, and the 5HT transporter. None of the treatments gave rise to significant changes in any of the mRNA levels at any time point. These results suggest that the reported changes in 5HT receptor numbers do not occur as a result of changes in the abundance of their encoding mRNAs, and that changes to the latter is not central to the therapeutic effects of antidepressant drugs.
Spurlock
G
G
Department of Psychological Medicine, University of Wales College of Medicine, Heath Park, Cardiff, U.K.
Buckland
P
P
O'Donovan
M
M
McGuffin
P
P
D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D001345:Autoradiography; D001483:Base Sequence; D001923:Brain Chemistry / Q000187:drug effects; D002352:Carrier Proteins / Q000378:metabolism*; D017403:In Situ Hybridization; D007536:Isomerism; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism*; D026901:Membrane Transport Proteins; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins; D015345:Oligonucleotide Probes; D012333:RNA, Messenger / Q000096:biosynthesis*; D051381:Rats; D017208:Rats, Wistar; D011985:Receptors, Serotonin / Q000096:biosynthesis*; D012701:Serotonin / Q000378:metabolism*; D050486:Serotonin Plasma Membrane Transport Proteins; D014365:Tryptophan Hydroxylase / Q000378:metabolism
D000928:Antidepressive Agents; D002352:Carrier Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D015345:Oligonucleotide Probes; D012333:RNA, Messenger; D011985:Receptors, Serotonin; D050486:Serotonin Plasma Membrane Transport Proteins; C493232:Slc6a4 protein, rat; D012701:Serotonin; D014365:Tryptophan Hydroxylase