John M. Beaton

In vivo metabolism of α,α,β,β-tetradeutero-n, N-dimethyltryptamine in rodent brain

The metabolism of alpha,alpha,beta,beta- tetradeutero -N,N -dimethyltryptamine ( D4DMT ) in rat brain in vivo as a function of time and dose was examined. Quantification of D4DMT and its respective deutero-metabolites was accomplished using gas chromatographic/mass spectrometric/selected ion monitoring/isotope dilution techniques. The results of this study indicate that D4DMT is metabolized to the corresponding deutero-N-methyltryptamine, tryptamine, 1,2,3,4-tetrahydro-beta-carboline, and 2-methyl-1, 2,3,4-tetrahydro-beta-carboline in rat brain. The subcellular distribution of D4DMT and the aforementioned metabolites is also reported.

Comparison of the brain levels of N,N-dimethyltryptamine and α,α,β,β-tetradeutero-N,N-dimethyltryptamine following intraperitoneal injection: The IN VIVO kinetic isotope effect

A comparison of the brain levels (microgram/g wet weight of tissue) of the hallucinogen N,N-dimethyltryptamine (DMT) and its deuterated analog alpha, alpha, beta, beta-tetradeutero-DMT (D4DMT) as a function of time and dose is reported. It was observed that the presence of deuterium in the alpha- and beta-positions of the ethylamine side-chain led to a potentiation of the level of DMT in brain. Strikingly different dynamics of uptake and clearance were also noted. We propose that these results are due to primary kinetic isotope effect, illustrating the importance of the alpha-position in the metabolism of DMT.

A comparison of the behavioral effects of proteo- and deutero-N, N-dimethyltryptamine

The behavioral effects of N,N-dimethyltryptamine (DMT) and α, α, β, β-tetradeutero-N,N-dimethyltryptamine (D4DMT) at dose levels of 2.5 and 5.0 mg/kg were examined in rats on a food reinforced schedule. The D4DMT was observed to produce a significantly greater disruption of behavior, have a longer duration of action and a shorter time to onset than DMT. This potentiation, apparently due to the kinetic isotope effect, suggests that DMT is significantly metabolized and deactivated by deamination at the α-position.

An investigation of the effects of l-methionine and related metabolites on rat behavior

l -Methionine, l -methionine plus l -serine, l -cysteine, l -serine, and betaine were tested on a modified discriminated Sidman avoidance schedule in rats. Daily injections of 250 mg/kg of these compounds were administered for at least 28 consecutive days. Schedule performance in the rat was monitored during this period and compared to preinjection saline controls. The results indicated that only methionine had significant behavior-disrupting effects. The disruption was removed by the addition of serine, suggesting that the methionine disrupting effect may have been due to one of the metabolites of methionine—homocysteine.

Ontogeny of N,N-Dimethyltryptamine and related indolealkylamine levels in neonatal rats

The present study deals with the measurement of the brain levels of the two potent hallucinogens N,N-dimethyltryptamine (DMT) and 5-methoxy-N,N-dimethyltryptamine (OMB), the biogenic amine tryptamine (TA), and its condensation product 1,2,3,4-tetrahydro-beta-carboline (THBC) in rats of various ages. Using gas chromatography-mass spectrometry with isotope dilution, we detected DMT, OMB, and THBC in neonatal rats from birth. DMT levels remained low until days 12 and 17 at which time they increased significantly and then returned to the initial low levels for all subsequent ages. The levels of OMB were higher than those measured for DMT with the highest levels being observed at days 12 and 17, and also on day 31. However, the levels for OMB showed much more variation. Although elevated levels of DMT and OMB have been correlated with stress, there are no known functions for these compounds. TA levels remained below detection limits until day 19. THBC levels were observed to be highest on days 22 and 31. The role that THBC plays in mammalian tissues is not known.

The effects of cholinergic agents on morphine-induced circling behavior in the intact mouse.

The effects of morphine on locomotor activity in mice was studied. It was shown that morphine in this species induces circling, a dose-dependent, stereotyped behavior. At high doses of morphine, mice engaged virtually exclusively in circling uninterrupted by other activities. The effect was modified by muscarinic agents. Blockade of muscarinic receptors with atropine potentiated circling while the muscarinic agonist, oxotremorine, attenuated it. The mixed muscarinic/nicotinic cholinergic agonist, physostigmine, had no effect on this behavior.

The schedule dependent effects of 3-quinuclidinyl benzilate on operant behavior in the rat

The effects of 3-quinuclidinyl benzilate (QNB) on performance maintained by a fixed-ratio 20 (FR-20) or a differential-reinforcement-of-low-rate 20 sec. (DRL-20) schedule for water reinforcement were studied in rats. Graded doses of QNB (range 0.0125-0.2 mg/kg) were administered IP immediately prior to 30 min test sessions. QNB had a biphasic effect on FR responding: at a low dose (0.0125 mg/kg) it increased, while at higher doses (0.05-0.2 mg/kg) it decreased mean response rate in a linear, dose-dependent, manner. QNB had only a monotonic effect on DRL responding; doses of 0.05-0.2 mg/kg increased the mean response rate and decreased reinforcement rate in a dose-related fashion. The ED50s for loss of reinforcement were identical (0.07 mg/kg) for both schedules. The findings indicate that QNB may exert rate dependent effects.

Facilitation of an operant task in the rat following injection of whole brain extract

It has been shown that the administration of trained donor brain extract to naive rats results in facilitation of performance on the same task. In the present study a group of food deprived rats was trained to press a lever for food on a continuous schedule of reinforcement until they reached criterion. The animals were then sacrificed, their brains excised, homogenized and the small proteins (m.w. less than 3500) extracted. A group of untrained rats was also sacrificed and their brains extracted. Three groups of rats were used as recipients, receiving either trained donor or untrained donor brain extract or saline. The animals were tested individually for one-hour sessions at 18, 42 and 66 hours after the injection. The number of bar presses made by each rat was noted and the group mean plus or minus the standard deviation were calculated for each session. The results of a one-way analysis of variance showed that the group which received trained donor brain extract performed at a higher rate than either control group. These data suggest that some factor, (specific or non-specific), associated with the task has been transferred.

Using NBME Subject Examinations as a Pretest to Identify Medical Students “At Risk” in a Behavioral Sciences Course

Pretesting students has been considered a sound educational practice but the reports of its utility in medical education are sparse. The purpose of the study was to demonstrate the usefulness of the NBME Subject Examination as a pretest to identify students “at risk” in a medical school behavioral sciences course. The results indicated that the pretest was helpful in documenting course effectiveness and that it and other measures could be used to provide an early prediction of students’ behavioral sciences course grades.