Chronic Electroconvulsive Seizures Increase the Expression of Serotonin2 Receptor mRNA in Rat Frontal Cortex

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Abstract
The present study examines the influence of electroconvulsive seizure (ECS), as well as antidepressant drugs, on levels of serotonin2 (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/μg 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 [3H]ketanserin ligand binding, confirming previous reports. Northern blot analysis demonstrated that 5‐HT2 receptor mRNA occurs as two bands (∼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 5‐HT2 receptor mRNA, although levels of [3H]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.