Stimulus properties of mescaline and N-methylated derivatives: Difference in peripheral and direct central administration

The purpose of this study was to examine the possibility that N-methylated derivatives of mescaline might produce interoceptive stimuli similar to mescaline. Rats were trained in a two-lever operant chamber to discriminate the dragged (mescaline, 25 mg/kg, i.p.) state from the non-drugged state (saline, i.p.). On session days following mescaline administration, only responses on the right lever of the operant chamber were reinforced and on days following saline only responses on the left lever were rewarded. The degree of discrimination between mescaline and saline was determined by the percentage of responding on the state appropriate lever during extinction. Following the acquisition of response control by i.p. mescaline, the subjects were tested for stimulus generalization after i.p. or intraventricular injections of various doses of mescaline, N-methylmescaline (NMM), N,N-dimethylmescaline (DMM), or saline. Intraventricularly administered mescaline exhibited a dose-dependent generalization to the cue produced by systemically injected mescaline, indicating a central nervous system locus of action. NMM demonstrated only saline responses regardless of the dose or route of administration. DMM at a dose of 50 mg/kg, i.p., generated responses characteristic of mescaline, suggesting a similarity in behavioral effects between DMM and mescaline. However, following intraventricular injection of DMM only a transient generalization to the mescaline state resulted. From these results it is concluded that NMM and DMM, two possible metabolites of mescaline, apparently do not play a significant role in the mescaline-induced internal stimuli.