Chronic electroconvulsive shock (ECS), a widely used treatment for intractable depression, increases the density of 5-HT2A receptor binding sites and mRNA in rat frontal cortex. In contrast, this treatment appears to have no significant effect on 5-HT-stimulated phosphatidyl inositol turnover in rat brain. To investigate the effect of chronic ECS on the 5-HT2 receptor family further, we determined its effects on head shakes and c-fos expression in the rat in response to the 5-HT2A/2C receptor agonist DOI [1-(2,5-dimethoxy-4-iodophenyl)-2-amino-propane]. Chronic ECS (5 electroconvulsive shocks over 10 days, via earclips under halothane anaesthesia) caused a significant enhancement in the number of head shakes counted in a 30 min period after administration of 2 or 8 mg/kg DOI. In contrast, this treatment had no effect on Fos expression, induced by either dose of DOI, in any region of rat forebrain examined. Fos expression was low-to-undetectable in the brains of animals treated with chronic ECS followed by saline and sham ECS animals that had been treated identically, but with no administration of electrocurrent. Thus the lack of any change in PI turnover, following chronic ECS administration, appears to be mirrored by the failure of this treatment to alter 5-HT2 receptor-mediated Fos expression.