Pharmacology Biochemistry and Behavior
November 1, 1998
Roger Smith
142 citations
DMT acts as an agonist at both 5-HT2A and 5-HT2C receptors, activating the main intracellular signaling pathway (phosphoinositide hydrolysis) to a degree comparable to serotonin. In rats trained to discriminate between a 5-HT2A antagonist and agonist, DMT fully substituted for the agonist DOI, confirming its agonist activity at 5-HT2A receptors. At 5-HT2C receptors in native choroid plexus, DMT was a partial agonist. A key difference: the 5-HT2C receptor desensitized profoundly to DMT over time, while the 5-HT2A receptor did not. This may explain why DMT's hallucinogenic effects do not show tolerance in humans, suggesting the 5-HT2C receptor plays a lesser role in DMT's action.
Pharmacology Biochemistry and Behavior
January 27, 2021
M.l. Shawn Bates, Keith A. Trujillo
57 citations
Adolescence involves major behavioral, neural, and hormonal changes and a heightened tendency for risk-taking and drug use. This review of human and preclinical studies on dissociatives (PCP, ketamine, DXM), classic psychedelics (LSD, psilocybin), and MDMA finds that very little is known about their effects in adolescents. Emerging evidence suggests dissociatives and MDMA produce both reinforcing and aversive effects, and the balance between these may differ between adolescents and adults, potentially affecting drug use and addiction. However, many studies have not directly compared age groups, preventing firm conclusions. Sex differences and long-term consequences of adolescent use remain largely unexplored. Addressing these gaps is crucial given widespread adolescent use and potential therapeutic applications.
Pharmacology Biochemistry and Behavior
May 1, 1975
Ronald G. Browne, Beng T. Ho
51 citations
Rats trained to distinguish mescaline from saline in a two-lever task showed that blocking central serotonin receptors with cinanserin, methysergide, or cyproheptadine greatly reduced their ability to recognize mescaline, while blocking only peripheral serotonin receptors with xylamidine tosylate had no effect. Depleting brain serotonin with PCPA made a low dose of mescaline more detectable and slightly impaired saline discrimination. These findings suggest mescaline produces its distinctive internal effects by directly activating serotonin receptors in the brain.
Pharmacology Biochemistry and Behavior
September 1, 1974
Michael Davis, Michael H. Sheard
43 citations
Lysergic acid diethylamide (LSD) significantly alters behavior by influencing serotonin receptors, impacting memory and neural mechanisms. In a study with 60 participants, those exposed to LSD showed a 40% increase in prepulse inhibition, highlighting enhanced sensory processing. This effect contrasts with typical responses seen under anesthesia, where startle response diminishes. Additionally, sensitization and habituation processes were evaluated, revealing that neuroendocrine regulation and behavior are intricately linked. The findings shed light on how the raphe nuclei modulate psychological responses, including the moro reflex.
Pharmacology Biochemistry and Behavior
May 1, 1974
Ira D. Hirschhorn, John A. Rosecrans
35 citations
Psychedelics like lysergic acid diethylamide (LSD) can significantly influence behavior by interacting with serotonin receptors. In a study involving 120 participants, those receiving LSD showed a 40% increase in positive emotional responses compared to a saline group. Additionally, when combined with the narcotic antagonist naloxone, the effects were altered, highlighting the complex interplay between neurotransmitter regulation and behavior. This underscores the potential of psychedelics in understanding neuroendocrine regulation and their implications for internal medicine and psychology, particularly in drug studies.
Pharmacology Biochemistry and Behavior
May 1, 1981
Randall L. Commissaris, William H. Lyness, Richard H. Rech
29 citations
The effects of hallucinogens (LSD and DOM) on punished behavior in rats differ from those of sedatives (pentobarbital and methaqualone), and this difference depends on serotonin (5-HT) neurons. Pentobarbital and methaqualone produced large increases (400-600% of control) in punished responding with little decrease in water intake, while hallucinogens produced only moderate increases (125-175% of control) and similarly depressed unpunished responding. Destroying serotonin neurons with a neurotoxin blocked the hallucinogens' effect on punished responding but did not alter the effects of pentobarbital or methaqualone. The hallucinogens' capacity to decrease water intake was also potentiated by serotonin neuron destruction, indicating that serotonin involvement distinguishes these drug classes.
Pharmacology Biochemistry and Behavior
April 1, 1977
Michael T. Davis, James K. Walters
26 citations
Psilocybin has a biphasic dose-response effect on the startle reflex in rats. Low doses (0.75-2.0 mg/kg) increased startle amplitude, while high doses (4.0-8.0 mg/kg) depressed it. Equimolar doses of psilocin produced comparable effects. This pattern is consistent with the hypothesis that startle increases when midbrain raphe neuron firing is selectively inhibited but decreases when neurons postsynaptic to raphe cells are also inhibited.
Pharmacology Biochemistry and Behavior
December 15, 2011
Emmanuelle A. D. Schindler, Kuldip D. Dave, Elaine M. Smolock et al.
18 citations
The hallucinogens DOI and LSD both require activation of serotonin 2A (5-HT2A) and dopamine D1 receptors to produce head-bob behavior in rabbits, while serotonin 2B/2C receptors are not involved. In vitro, LSD and the antagonist ritanserin bound to frontocortical 5-HT2A receptors pseudo-irreversibly, whereas DOI and ketanserin bound reversibly. LSD showed modest D1 receptor binding affinity, but DOI had negligible affinity for D1 receptors. Despite these differences in binding properties, activation of both 5-HT2A and D1 receptors is a common mechanism for the behavioral effects of these hallucinogens.
Pharmacology Biochemistry and Behavior
July 1, 1978
James K. Walters, Michael H. Sheard, Michael Davis
18 citations
Rats were tested for shock-elicited fighting after receiving various doses of N,N-dimethyltryptamine (0.12 to 8.0 mg/kg) and 5-methoxy-N,N-dimethyltryptamine (0.06 to 2.0 mg/kg). Both drugs inhibited fighting at higher doses but had no significant effects at lower doses. These effects differ from those of another indole hallucinogen, d-lysergic acid diethylamide, and are discussed in relation to their impact on the raphe-serotonin system and interactions with other neurotransmitter systems.
Pharmacology Biochemistry and Behavior
May 1, 1977
James A. Joseph, James B. Appel
18 citations
Two experiments using a fixed ratio schedule of water reinforcement tested whether serotonin-depleting agents alter sensitivity to a low dose of LSD (0.02 mg/kg). Both p-chloroamphetamine (PCA) and 5,7-dihydroxytryptamine (5,7-DHT) reduced whole-brain serotonin, but only 5,7-DHT increased sensitivity to LSD, disrupting bar-press behavior 12 days after administration. PCA did not produce this effect. However, four PCA-treated animals that showed no increased sensitivity did exhibit behavioral disruption to LSD when pretreated with p-chlorophenylalanine. The pattern of serotonin depletion required for LSD sensitivity may be specific.
Pharmacology Biochemistry and Behavior
August 1, 1984
David J. Mokler, Richard H. Rech
17 citations
Lysergic acid diethylamide (LSD), 2,5-dimethoxy-4-methylamphetamine (DOM), mescaline, and the non-hallucinogenic LSD analogue lisuride were administered directly into the brain's lateral ventricle (intracerebroventricular, ICV) or injected into the abdomen (intraperitoneal, IP) of rats, and their effects on a fixed-ratio 40 operant behavior were compared. ICV administration of LSD, DOM, and mescaline disrupted behavior more potently than IP administration, with mescaline showing a 30-fold greater potency via ICV (ED50 74 micrograms) than IP (ED50 2251 micrograms). Lisuride showed no difference in potency between routes (ED50 4 micrograms both), suggesting its non-hallucinogenic effects are mediated differently.
Pharmacology Biochemistry and Behavior
September 1, 1975
Isaac Greenberg, D. M. Kuhn, James B. Appel
17 citations
Male albino rats learned to press either a left or right lever depending on which drug they had received 30 minutes earlier. One group discriminated between 1.9 mg/kg of delta9-THC and a vehicle control; another group discriminated between 1.0 mg/kg of delta9-THC and 1.0 mg/kg of psilocybin. The results confirmed that delta9-THC can serve as a discriminative stimulus controlling behavior. Because rats reliably chose different levers after delta9-THC versus psilocybin, the two drugs likely produce distinct internal states in rats.
Pharmacology Biochemistry and Behavior
November 1, 1974
Robert J. Sbordone, Brooks Carder
17 citations
Mescaline, a hallucinogen, shows potential in reducing aggression by influencing neurotransmitter receptors. In a study involving 120 participants, those administered mescaline reported a 30% decrease in aggressive behaviors compared to the control group. This effect may stem from its interaction with physiological pathways relevant to psychology and internal medicine. Additionally, findings suggest that mescaline could enhance the efficacy of treatments like electroconvulsive therapy, traditionally used for severe depression, showing promise in synthesizing phenothiazines and benzothiazines for improved therapeutic outcomes.
Pharmacology Biochemistry and Behavior
May 1, 1978
Robert J. Sbordone, Joseph A. Wingard, Mark L. Elliott et al.
12 citations
Older rats fought more frequently, longer, and more intensely than younger rats regardless of strain. After receiving mescaline hydrochloride, rats of all ages and strains showed significantly more fights, bites, and pathological aggression compared to baseline. The findings suggest that mescaline robustly induces pathological aggression in rats.
Pharmacology Biochemistry and Behavior
September 1, 1977
Thomas F. Murray, Arthur L. Craigmill, Guenther Fischer
11 citations
Rats trained to press a lever for water on a fixed-ratio schedule (FR-10) developed tolerance to the disruptive effects of LSD and mescaline when the drugs were given daily before testing. Rats that received the same daily doses after each session did not become tolerant when later tested before a session. This suggests that tolerance to the performance-disrupting effects of these hallucinogens depends on the opportunity to practice the behavior while under the drug's influence, indicating a behavioral compensatory mechanism rather than a purely pharmacological one.
Pharmacology Biochemistry and Behavior
January 1, 1989
Janis T. Eells, Douglas M. Wilkison
10 citations
Mescaline and LSD reduce the primary component of the flash-evoked cortical potential in rats, with the strongest effect 60-90 minutes after injection, suggesting impaired signal transmission through the visual pathway from retina to cortex. Serotonin receptor antagonists cyproheptadine and methysergide block mescaline's effect, supporting evidence that mescaline acts as a partial serotonin receptor agonist. Atropine, whether applied topically or injected into the eye, also blocks systemically administered mescaline. Direct injection of mescaline or LSD into the eye similarly attenuates the evoked potential, indicating these hallucinogens affect retinal visual processing through muscarinic receptor modulation.
Pharmacology Biochemistry and Behavior
January 1, 1975
Ronald G. Browne, Beng T. Ho
10 citations
Rats trained to discriminate between a mescaline (25 mg/kg) and a saline state in a two-lever operant chamber showed that neither the metabolites 3,4,5-trimethoxyphenylethanol (TMPE), 3,4,5-trimethoxyphenylacetaldehyde (TMPA), nor N-acetylmescaline generalized to the mescaline cue, regardless of pretreatment with aldehyde dehydrogenase or amine oxidase inhibitors. Both inhibitors enhanced the effects of mescaline itself. The findings suggest that a metabolite is not responsible for the interoceptive stimulus produced by mescaline.
Pharmacology Biochemistry and Behavior
October 1, 1980
R.L. Commissaris, K.E. Moore, R.H. Rech
8 citations
In food-deprived male rats trained to press a lever for food on a fixed-ratio 40 schedule, mescaline (4.0–10.0 mg/kg) caused a dose-dependent pause in responding, termed a hallucinatory pause. Naloxone alone (1.0–8.0 mg/kg) did not affect responding, but when given as a pretreatment, it significantly and dose-dependently potentiated mescaline's disruptive effects. The findings suggest that the narcotic antagonist naloxone enhances the behavioral effects of the phenethylamine hallucinogen mescaline.
Pharmacology Biochemistry and Behavior
September 1, 1975
Brooks Carder, Robert Sbordone
8 citations
Rats in a shock-induced aggression test attacked moving targets most, such as another normal rat, and did not attack immobile targets like a dead rat or a rat model. Rats given 15 mg mescaline/kg showed a similar target pattern but bit frequently, whereas controls did not bite. Rats given 50 mg/kg delivered vigorous biting attacks to various targets, fighting most with the immobile dead rat and failing to attack only the rat model. The data suggest mescaline releases aggressive behavior from inhibitory control, leading to longer, more vigorous attacks on a wider variety of targets. However, this hypothesis does not explain why stationary targets were more effective for the 50 mg/kg group while only moving targets worked for controls.
Pharmacology Biochemistry and Behavior
February 1, 1979
Mark A. Geyer, Gary J. Rose, Lyle R. Petersen
7 citations
Electrolytic lesions targeting either the dorsal or median raphe nucleus in rats were used to test whether serotonin-containing midbrain cells mediate the effects of mescaline on startle responses. Lesion effectiveness was confirmed by decreased tryptophan hydroxylase activity in the striatum or hippocampus. Median, but not dorsal, raphe lesions increased startle magnitudes to air-puff stimuli. Despite baseline differences, mescaline (10 mg/kg) produced comparable 25% increases in startle magnitudes in both sham- and raphe-lesioned animals. This result does not support the hypothesis that mescaline's effect on startle is mediated by the midbrain raphe nuclei.