The time-dependent stimulus effects of R(-)-2,5-dimethoxy-4-methamphetamine (DOM): implications for drug-induced stimulus control as a method for the study of hallucinogenic agents

The pharmacodynamic characteristics of the stimulus effects of the hallucinogensd-LSD and (–)DOM were investigated in the rat. The stimulus control induced by (–)DOM (0.56 mg/kg) was significantly less stable at the 15-min pretreatment time than at the 75-min pretreatment time. In addition, (–)DOM (0.8 mg/kg) produced a time-dependent substitution for the LSD stimulus in LSD trained subjects (0.1 mg/kg, 15-min pretreatment time). As pretreatment times were increased, the substitution of (–)DOM (0.8 mg/kg) for the LSD stimulus increased, culminating in a maximal level of 99.5% LSD-appropriate responding at the 75-min pre-treatment time. A dose-response relationship for the substitution of (–)DOM (75-min pretreatment time) for the LSD stimulus, indicated that 0.2 mg/kg (–)DOM was the minimum dose which elicited greater than 90% LSD-appropriate responding. LSD (0.32 mg/kg, 15-min pretreatment time) fully substituted for (–)DOM in the (–)DOM trained subjects (0.56 mg/kg, 75-min pretreatment time). These findings suggest that the pharmacodynamic parameters ofd-LSD and (–)DOM-induced stimulus control differ. The time of onset for the stimulus effects of (–)DOM is markedly longer than that of LSD in the rat.This study was supported in part by U.S. Public Health Service grant DA 03385 [J.C.W., R.A.R.], by National Research Service Award MH 10567 [D.F.], and by a fellowship from Schering-Plough Research Institute [D.F.]. Animals used in these studies were maintained in accordance with the Guide for Care and Use of Laboratory Animals of the Institute of Laboratory Animal Resources, National Research Council