Evidence for a functional interaction between 5-HT1A and 5-HT2 receptors in rats

Evidence of a functional interaction between serotonin 5-HT1A and 5-HT2 receptor subtypes has been compromised by incomplete experimental designs and conflicting data. To test for such an interaction, combinations of the 5-HT1A agonist 8-OH-DPAT and the 5-HT2 agonist DOI were administered to rats prior to testing of locomotor activity in the Behavioral Pattern Monitor (BPM). The BPM is an activity and holeboard chamber that enables analyses of quantitative and qualitative changes in locomotor and investigatory activity. Dose-response studies of 8-OH-DPAT and DOI alone and in the presence of selected doses of the other drug were performed in order to allow isobolographic analysis, which characterizes the relationship of two drugs as either additive (no interaction), supra-additive, or infra-additive. Rats treated with saline, 8-OH-DPAT (6.25, 12.5, 25, or 50 microg/kg SC), DOI (0.15, 0.3, or 0.6 mg/kg SC), or selected combinations of both drugs were tested in the BPM for 1 h. Isobolographic analysis of the effects on locomotor activity revealed that 8-OH-DPAT and DOI interact in an infra-additive manner. Thus, at a functional level, 5-HT1A and 5-HT2 receptors interact antagonistically in the modulation of locomotor activity.