2.5 Dose-Response Effects of 5-HT2A/2C Agonists on Behavior

Separate cohorts of 12 rats were used to determine dose-response effects for DOI, 25C-NBOMe, 25I-NBOMe, 2C-C and 2C-I (60 rats total). Rats in each cohort were tested once per week for 4 consecutive weeks, until the 5 dose groups for the drug of interest (vehicle plus 4 drug doses) reached a completed N=9 rats/group (i.e., total N=45). At each test session, rats received a single sc injection of drug or vehicle, and doses were randomly assigned, with the exception that rats receiving the highest drug dose always received vehicle treatment the following week. On test days, groups of rats were moved to the testing room in their home cages and given 1 h to acclimate. Feeding trays were removed, and wire lids were placed atop the cages. For the DOI experiments, rats received 0 (saline), 0.03, 0.1, 0.3 or 1.0 mg/kg doses; for the 25C-NBOMe and 25I-NBOMe experiments, rats received 0 (saline), 0.01, 0.03, 0.1 or 0.3 mg/kg doses; and for the 2C-C and 2C-I experiments, rats received 0 (saline), 0.1, 0.3, 1.0, or 3.0 mg/kg doses. Immediately before vehicle or drug injection and at 15, 30, 45, 60, 75, 90, 105 and 120 min post-injection, animals were observed for 90 sec and body temperatures were measured with the handheld reader. For behavioral scoring, the number of WDS and BMC were counted during the 90-sec observation period by an experienced rater who was not blind to the treatments. WDS were defined as rapid shaking of the head, neck and trunk from one side to the other, analogous to a wet dog shaking to dry itself, whereas BMC were defined as brief contractions of the paraspinal back muscles which elicit movement of the skin in a tail to head direction (Pranzatelli, 1990; Canal and Morgan, 2012). Rats were given summed scores for WDS and BMC which were totaled from all eight observation periods, as previously described (Baumann and Rothman, 1996).