Discriminative stimulus properties of the serotonergic agent 1-(2, 5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI)

Abstract

Using a two-lever drug discrimination procedure, six rats were trained to discriminate 0.5 mg/kg of racemic 1-(2, 5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) from saline. Once trained, the animals demonstrated a dose-related decrease in discriminative performance upon administration of lower doses of DOI (ED50 = 0.16 mg/kg). DOI-stimulus generalization occured with the putative 5-HT 2 agonist DOM (ED50 = 0.49 mg/kg), but not with the 5-HT 1A agonist 8-OH DPAT, or the 5-HT 1B agonist TEMPP. Furthermore, the DOI stimulus could be antagonized by pretreatment of the animals with the 5-HT 2 antagonist ketanserin. The present results, coupled with the prior demonstration that DOI possesses a significant affinity and selectivity for 5-HT 2 binding sites, suggest that the discriminative stimulus effects of DOI may be 5-HT 2-mediated.