by dimitri novusDouble-blind scientists extensively dosing rodents and primates report finding disruption of conditioned behavioral programs and other metaprogrammatically useful anomolies.
BROWER, KIRK J; SIEGEL, RONALD KHyperspace CHEM
Hallucinogen-induced behaviors of free-moving chimpanzees.
Bulletin of the Psychonomic Society; 1977 Apr Vol 9(4) 287-290
Studied the effects of the hallucinogen N,N-dimethyltryptamine (DMT) on the behavior of 2 island groups of 4 chimpanzees ( Pan troglodytes ) each. One target S from each group was selected for treatment, and individual and social behaviors were scored according to a quantitative observational system. Low doses of DMT (.5-3.0 mg/kg) caused dose-dependent increases in duration of vocalization, fear grimace, and locomotion. Higher doses (4.0 mg/kg) tended to decrease these behaviors as well as others such as self-grooming. Social aggregation tended to decrease with increasing doses, and social interactions between target Ss and others were rare. Results tend to support the hypothesis that hallucinogens increase social spacing and isolation.
COOPER, STANLEY G; SCHIFF, STANLEY R; BRIDGER, WAGNER H
Tolerance to behavioral effects of N,N -dimethyltryptamine in mice.
Biological Psychiatry; 1981 Sep Vol 16(9) 861-867
48 albino mice were Ss in 3 experiments designed to test (1) whether or not a once-daily administration of dimethyltryptamine (DMT) would result in tolerance to its behavioral effects and (2) the possibility that daily exposure to DMT would result in classical conditioning. Experiments differed only in the concentration of DMT used--4, 8, or 12 mg/kg. Dose effects were noted for variables including staring and head movement, indicating specific behavioral effects due to developed tolerance. No classically conditioned DMT-induced behavior was noted.
DAVIS, MICHAEL; SHEARD, MICHAEL H
Biphasic dose-response effects of N-N-dimethyltryptamine on the rat startle reflex.
Pharmacology, Biochemistry and Behavior; 1974 Nov-Dec Vol 2(6) 827-829
Measured the startle reflex in 4 groups of 10 male Sprague-Dawley albino rats each after intraperitoneal injection of saline or .12, .25, .50 or 4.0 mg/kg N-N-dimethyltryptamine (DMT). Low doses (.25 and .50) of DMT augmented startle, but the high dose (4.0) depressed startle. This biphasic dose-response relationship is consistent with the hypothesis that startle is enhanced when midbrain raphe neurons are inhibited but depressed when cells postsynaptic to raphe neurons are also inhibited.
FILE, SANDRA E
Effects of N,N-dimethyltryptamine on behavioural habituation in the rat.
Pharmacology, Biochemistry and Behavior; 1977 Feb Vol 6(2) 163-168
Studied the processes involved in habituation and the various ways drugs might affect habituation in 2 experiments with a total of 157 male hooded rats. Exploration was measured in a holeboard. N,N-Dimethyltryptamine (DMT, 4 mg/kg) profoundly reduced the level of exploration, precluding any conclusions about the rate of habituation with this dose. However, both 2 and 4 mg/kg doses prevented the 24-hr retention of habituation of exploration. DMT (2 and 4 mg/kg) did not reduce the initial distraction to a tone stimulus, but the rate of habituation and its 24-hr retention was impaired.
KOVACIC, BEVERLY; DOMINO, EDWARD F
Tolerance and limited cross-tolerance to the effects of N,N-dimethyltryptamine (DMT) and lysergic acid diethylamide-25 (LSD) on food-rewarded bar pressing in the rat.
Journal of Pharmacology and Experimental Therapeutics; 1976 Jun Vol 197(3) 495-502
Adult male Holtzman rats trained to barpress for milk reward on a 4-response FR schedule were given ip injections of 3.2 or 10 mg/kg of N,N-dimethyltryptamine (DMT) every 2 hrs for 21 days. Every 24 hrs Ss were placed in operant chambers for 30 min before a scheduled injection and were left in the chambers for 30-80 min after injection. During the 1st wk of chronic treatment, daily barpressing worsened progressively until the 6th day of the series, at which time Ss in the 10 mg/kg group did not barpress at all. As the chronic injections continued, rates of barpressing gradually increased until responding was not disrupted at all by DMT. Ss in the 3.2 mg/kg group showed cross-tolerance to LSD (0.1 mg/kg). Another group of Ss was made partially tolerant to the disruptive effects of LSD (0.1 mg/kg, ip) on barpressing with a series of injections given 1/day for 21 days and then 3 times/day for the next 4 days. Cross-tolerance was not demonstrated to a challenge injection of 10 mg/kg of DMT. When LSD injections were continued for another 3-5 days until the Ss were completely tolerant to LSD, they displayed cross-tolerance to 302 mg/kg of DMT.
KOVACIC, BEVERLY; WANG LU, LEE JANE; RUFFING, DIANE; DOMINO, EDWARD F
Interactions of partial LSD analogs with behavioral disrupting effects of LSD and DMT in the rat.
European Journal of Pharmacology; 1978 Jan Vol 47(1) 37-44
Trained male Holtzman rats to barpress on an FR schedule whereby every 4th press earned a reward of 0.01 ml of sugar-sweetened milk. After ip injection of LSD (0.1 mg/kg) or dimethyltryptamine (3.2 or 10 mg/kg) such barpressing was abolished completely and resumed, usually within an hour, at a rate near the preinjection control rate of pressing. It continued at a steady pace until Ss were removed from the operant chamber 30 min later. A series of N,N-diethylnipecotamide derivatives were synthesized and tested for their ability to modify the disruptive effect of these hallucinogens. N,N-diethylbutyramide and 1-methyl-1,2,5,6-tetrahydropyridine-3-(N,N-diethylcarboxamide) were also tested. Pretreatment with a single ip injection of any of these compounds (5-40 mg/kg) either had no effect on or else prolonged the duration of hallucinogen-induced cessation of barpressing.
SBORDONE, ROBERT J; WINGARD, JOSEPH A; GORELICK, DAVID A; ELLIOTT, MARK L
Severe aggression in rats induced by mescaline but not other hallucinogens.
Psychopharmacology; 1979 Dec Vol 66(3) 275-280
100 pairs of male Sprague-Dawley rats were administered mescaline; LSD; psilocin, N,N-dimethyltryptamine (DMT); 3,4-dimethoxyphenylethylamine (DMPEA); or 5-hydroxydopamine (5-OHDA) ip prior to being placed in a shock-elicited aggression situation. When footshock was delivered, controls struck each other with their forepaws but never engaged in either biting or injurious fighting. Mescaline-treated Ss (50 or 250 mg) rarely struck each other but engaged in nearly lethal biting. While LSD (25-400 mug/kg), psilocin (2.0 mg/kg), and DMT (5 mg/kg) produced some biting, this did not significantly differ from controls and never resulted in injuries. At higher doses, psilocin, DMT, and DMPEA decreased the amount and intensity of fighting. Ss treated with 5-OHDA (8-200 mg/kg) or LSD (25-400 mug/kg) did not differ from controls. Results suggest that mescaline's ability to induce pathological aggression in rats exposed to footshock is not shared by other hallucinogens or nonhallucinogenic mescaline analogs.
SCHLEMMER, R FRANCIS; NARASIMHACHARI, NEDATHUR; THOMPSON, VALERIE D; DAVIS, JOHN
The effect of a hallucinogen, 5-methoxy N,N-dimethyltryptamine, on primate social behavior.
Communications in Psychopharmacology; 1977 Vol 1(2) 105-118
Studied the behavioral effects of a hallucinogen, 5-methoxy N,N-dimethyltryptamine (5-MeODMT), following acute and chronic im administration of the substance to 2 selected members of a Stumptail macaque social colony of adult female monkeys. Injection of 5-MeODMT in 5-250 mg/kg doses caused dose-dependent induction of abnormal behavior and attenuation of normal affiliative behavior. Abnormal behavior induced by 5-MeODMT included dog-like 'wet shakes,' involuntary limb jerks, stereotyped behavior, and hypervigilance. 5-MeODMT induced dose-dependent decreases in social grooming and social activity, while self-grooming either increased or remained unchanged. Dose-dependent increases in submissive gestures were also seen. Chronic administration of 250 mg/kg for 12 days induced similar abnormal behavior and alterations of normal behavior. No definite signs of tolerance to any of these behavioral changes could be detected throughout the 12-day period. Similarities of 5-MeODMT-induced behavioral changes in monkeys to the effects of this and other hallucinogens in humans are discussed. It is suggested that primate social colonies may offer an excellent paradigm to study the behavioral effects of hallucinogens as well as other psychotomimetics.
SCHOENFELD, RONALD I
Lysergic acid diethylamide- and mescaline-induced attenuation of the effect of punishment in the rat.
Science; 1976 May Vol 192(4241) 801-803
At a dose as low as 1 mcg/kg, LSD significantly decreased the suppressive effect of electric shock on licking behavior in male albino Sprague-Dawley rats. Attenuation of punishment was also obtained with mescaline, but neither dimethyltryptamine nor Delta9-tetrahydrocannabinol was active in this test. Cyproheptadine and alpha-propyldopacetamide, drugs that interfere with the function of neurons that contain serotonin, had a behavioral effect similar to that of LSD and mescaline, which suggests that the attenuation of punishment produced by these hallucinogens may result from decreased activity of such neurons.
SIEGEL RK; BREWSTER JM; JOHNSON CA; JARVIK ME
The effects of hallucinogens on blind monkeys.
International Pharmacopsychiatry; 1976 Vol 11(3) 150-156
Studied 2 blind male macaque monkeys, using an observational profile that previously was shown to distinguish the effects of hallucinogens from those of other classes of drugs. LSD and dimethyltryptamine could be distinguished from saline, chlorpromazine, dextroamphetamine sulfate, and bromo-LSD by the increased frequency of spasms, stereotypy, bump, and tracking. The hallucinogens also produced dramatic increases in exploration and related behaviors normally seen only in response to real visual or auditory stimuli. These behaviors are discussed in terms of their similarity to behaviors observed with sighted monkeys in light and dark environments.
SIEGEL, RONALD K; JARVIK, MURRAY E
DMT self-administration by monkeys in isolation.
Bulletin of the Psychonomic Society; 1980 Aug Vol 16(2) 117-120
Three rhesus monkeys trained to smoke lettuce cigarettes for water reward extinguished responding when given water ad lib or when the hallucinogen dimethyltryptamine (DMT) was added to the lettuce. Ss were then individually confined to an operant unit placed in a sensory isolation chamber that deprived them of light and sound but permitted infrared video monitoring. After continuous isolation for several days, 2 Ss consistently self-administered DMT in performance marked by dramatic changes in perceptual-motor behaviors. These results suggest that animals will self-administer a hallucinogen when it provides stimulation in an otherwise deprived environment.
STOFF, DAVID M; MOJA, EGIDIO A; GILLIN, J CHRISTIAN; WYATT, RICHARD J
Disruption of conditioned avoidance behavior by N,N-dimethyltryptamine (DMT) and stereotype by b-phenylethylamine (PEA): Animal models of attentional defects in schizophrenia.
Journal of Psychiatric Research; 1978 Vol 14(1-4) 225-240
Describes 2 separate drug-induced behaviors in the rat that satisfy some criteria that should be met for animal models of schizophrenia. DMT, which is present in man although in extraordinarily small quantities, disrupts a simple learned behavior. The rat cannot adjust to repeated administration of DMT (it does not become tolerant) and, like the schizophrenic, performs better when given neuroleptics. PEA, which is also present in human tissue, forces the rat into a limited repertoire of behaviors (stereotypy). Again, repeated administration of PEA in the presence of decreased MAO does not induce tolerance, and stereotypy is blocked by neuroleptics. The 2 models are particularly germane because they deal with substances that are potential endogenous agents of schizophrenia.
WALTERS, JAMES K; SHEARD, MICHAEL H; DAVIS, MICHAEL
Effects of N,N-dimethyltryptamine (DMT) and 5-methoxy-N,N-dimethyltryptamine (5-MeODMT) on shock elicited fighting in rats.
Pharmacology, Biochemistry and Behavior; 1978 Jul Vol 9(1) 87-90
316 male albino rats were tested for shock-elicited fighting under various doses of DMT (0.12, 0.25, 0.50, 1.0, 4.0, and 8.0 mg/kg) 5-MeODMT (0.06, 0.12, 0.5, and 2.0 mg/kg). Both drugs produced an inhibition of fighting at higher doses but no significant effects at lower doses. The effects of the drugs on shock-elicited fighting, as well as on other behaviors, thus differ from those of another indole hallucinogen, LSD; findings are discussed in relation to their effects on single unit activity of the raphe-serotonin system and their interaction with other neurotransmitter systems.