Effect of the selective 5-HT receptor agonists 8-OHDPAT and DOI on behavior and brain biogenic amines of rats

Abstract

1. The behavioral responses, as well as the biogenic amines and metabolite contents in discrete brain areas were determined in male rats subcutaneously treated with a 5-HT1A (8-OHDPAT) or 5-HT2A (DOI) agonist at doses (0.5-2 mg/kg) sufficient to produce the typical effects of the stimulation of these brain receptor subtypes. 2. Besides the expected effects (i.e., forepaw treading, flat body posture and inhibition of 5-HT release and turnover), 8-OHDPAT displayed signs of increased dopaminergic transmission. 3. DOI increased dopamine turnover and provoked stereotypical behavior, in addition to head shakes and body twitches. 4. Moreover, DOI induced both forepaw treading and flat body posture, which are believed to be typical responses to the stimulation of brain 5-HT1A receptors. 5. This finding cannot be explained on the basis of actual knowledge, because the affinity of DOI for 5-HT1A receptor has been found to be very low, whereas indirect mechanisms of activation of this receptor subtype triggered by stimulation of 5-HT2A receptor are actually unknown.