CHRONIC ELECTROCONVULSIVE SEIZURES INCREASE THE EXPRESSION OF SEROTONIN(2) RECEPTOR MESSENGER-RNA IN RAT FRONTAL-CORTEX

The present study examines the influence of electroconvulsive seizure (ECS), as well as antidepressant drugs, on levels of serotonin, (5-HT2) receptor mRNA in rat frontal cortex. Using a sensitive RNase protective assay, preliminary studies demonstrated the predicted regional distribution for the 5-HT2 receptor mRNA: levels of 5-HT2 mRNA were highest in frontal cortex (2.58 amol/mug of total RNA), intermediate in neostriatum, thalamus, and midbrain, and lowest in hippocampus, cerebellum, and choroid plexus. Chronic (10 or 14 days), but not acute (1 or 3 days), ECS treatment significantly increased levels of 5-HT2 receptor mRNA. ECS treatment resulted in a similar time-dependent up-regulation of 5-HT2 receptor ligand binding; chronic, but not acute, ECS treatment significantly increased levels of [H-3]ketanserin ligand binding, confirming previous reports. Northern blot analysis demonstrated that 5-HT2 receptor mRNA occurs as two bands (approximately 5 and 6 kb in size), both of which were increased by chronic ECS treatment. The influence of antidepressant drug treatments on 5-HT2 receptor mRNA was also examined. Chronic fluoxetine treatment increased levels of 5HT2 receptor mRNA, although levels of [H-3]ketanserin ligand binding were not altered. In contrast, chronic administration of imipramine, mianserin, and tranylcypromine, treatments that decreased ligand binding, did not decrease levels of 5-HT2 receptor mRNA. In fact, mianserin treatment caused a small, but significant, increase in levels of receptor mRNA. The results suggest that ECS up-regulation of 5-HT2 receptor mRNA could underlie the increased density of 5-HT2 receptor binding sites in response to this treatment, but that other mechanisms likely operate in the down-regulation of 5-HT2 receptor ligand binding by antidepressant drug treatments.