Brain Research
April 15, 2011
Jonathan Smallwood, Kevin Brown, Ben Baird et al.
394 citations
The ability to generate and sustain an internal train of thought independent of external reality frees an agent from acting only on immediate environmental events. This paper proposes that such thought arises from cooperation between autobiographical information from the default mode network and a frontal-parietal control network that sustains and buffers internal trains of thought against disruption. This hypothesis explains two features: first, access to the top-down control system is a prerequisite of conscious experience, explaining why its activation and default mode activity are often observed together during internally guided thought.
Brain Research
June 3, 2011
Gennady G. Knyazev, Jaroslav Y. Slobodskoj-Plusnin, Andrey V. Bocharov et al.
261 citations
The default mode network (DMN), typically studied with PET and fMRI, has inconsistent support in EEG research. This study tested whether blind decomposition methods could identify DMN-like spatial patterns in EEG data across traditional frequency bands, and whether those patterns relate to task demands. Data were collected during rest, an explicit facial affect judgment task, and a social game task. Only alpha band patterns overlapped substantially with the DMN and correlated with DMN-related functions. Spontaneous self-referential thoughts during rest were linked to enhanced alpha activity in the posterior DMN hub, while processing external stimuli disrupted this activity and caused partial alpha phase-locking. This suggests alpha oscillations primarily synchronize internal mental processes rather than processing external stimuli.
Brain Research
September 1, 1975
James P. Bennett, Solomon H. Snyder
166 citations
D-LSD binds to rat brain membranes with high affinity and stereospecificity; the psychotropically inactive L-LSD is 1000 times weaker. 2-bromo-LSD, though psychotropically inactive, displaces D-LSD as potently as D-LSD. Serotonin is the only neurotransmitter with affinity for the LSD binding site. Destroying presynaptic serotonin neurons does not alter LSD binding, suggesting the binding site is post-synaptic. Regional distribution in monkey brain shows LSD binding correlates partly with serotonin uptake, but cortical areas are highest in binding and only intermediate in uptake.
Brain Research
October 1, 1990
Christopher J. Schmidt, Christine K. Black, Gina M. Abbate et al.
132 citations
In rats, MDMA caused a significant rise in body temperature (hyperthermia) that was competitively blocked by the selective 5-HT2 antagonist MDL 11,939. This antagonist also prevented MDMA-induced neurotoxicity, measured by reduced serotonin (5-HT) levels one week later. At higher MDMA doses, MDL 11,939 still fully protected against neurochemical deficits but only partially reduced hyperthermia, dissociating the two effects. Haloperidol did not affect MDMA-induced hyperthermia but did block long-term neurochemical effects. A selective serotonin reuptake inhibitor, MDL 27,777, did not alter hyperthermia from high-dose MDMA but completely prevented serotonin depletion. Preventing hyperthermia by lowering ambient temperature also blocked neurochemical changes. The results indicate that while the tested drugs do not counteract neurotoxicity by affecting temperature, hyperthermia may contribute to MDMA's long-term neurochemical effects.
Brain Research
August 27, 2004
John W. Muschamp, Meredith J. Regina, Elaine M. Hull et al.
116 citations
Hallucinogens such as LSD and DOM increase extracellular glutamate in the prefrontal cortex of rats, as shown by in vivo microdialysis. LSD (0.1 mg/kg) caused a time-dependent rise in glutamate that was blocked by a 5-HT(2A) antagonist. DOM (0.6 mg/kg) raised glutamate to 206% above controls. Direct application of LSD to the prefrontal cortex via reverse dialysis also rapidly increased glutamate, which remained elevated after infusion stopped. These findings suggest that enhanced glutamate release is a shared mechanism in the action of hallucinogens.
Brain Research
August 1, 1975
M. Da Prada, A. Saner, W.p. Burkard et al.
71 citations
Lysergic acid diethylamide (LSD) stimulates dopamine receptors in the central nervous system, which may contribute to LSD-induced psychosis. In rats, LSD decreased striatal and retinal homovanillic acid levels without changing dopamine levels, but delayed the disappearance of dopamine after a-methyl-p-tyrosine treatment. In cats, LSD reduced dopamine output into the caudate nucleus perfusate. Additionally, LSD increased adenylate cyclase activity in rat striatal homogenates. These findings suggest that dopamine receptor stimulation is involved in the effects of LSD.
Brain Research
August 1, 1975
Kern von Hungen, Sidney Roberts, Diane F. Hill
70 citations
D-lysergic acid diethylamide (D-LSD) and other serotonin antagonists block the activation of adenylate cyclase by norepinephrine or dopamine in cell-free preparations from rat brain. In the corpus striatum, D-LSD not only blocks dopamine's effect but also stimulates adenylate cyclase activity on its own, acting as an agonist at dopamine and serotonin receptors. This activation is blocked by dopamine-blocking agents like haloperidol and by serotonin-blocking agents, but not by propranolol. The findings suggest D-LSD can both activate and block dopamine, norepinephrine, and serotonin receptors in the brain.
Brain Research
February 1, 1990
E.C. Azmitia, R.B. Murphy, P.M. Whitaker-Azmitia
68 citations
The S(+) enantiomer of MDMA is ten times more potent than the R(-) enantiomer at inhibiting the development of serotonin uptake capacity in fetal rat raphe neurons. Both calcium-dependent and calcium-independent release of serotonin contribute to MDMA's toxic effect on these neurons, with the direct, transporter-mediated release being the first step. The serotonin 5-HT2 receptor, linked to increased intracellular calcium, is involved, as the antagonist ketanserin attenuates the effect of S(+)-MDMA. These findings clarify the cellular mechanisms of MDMA's serotonergic neurotoxicity.
Brain Research
March 25, 2003
Michael T. Williams, Laronda L. Morford, Sandra L. Wood et al.
66 citations
Rats given MDMA from postnatal days 11 to 20 showed lasting deficits in spatial learning and memory, even when growth restriction from the drug was matched by raising rats in larger litters. Males exposed to MDMA took longer and made more errors in the Cincinnati water maze than control males. In the Morris water maze, MDMA-treated rats of both sexes were impaired during initial learning. Only females showed deficits when the platform was first moved, but both sexes were impaired after a second move with a smaller platform. No differences appeared in swimming ability, cued navigation, or stress hormone responses. Growth retardation, injections, or litter size did not account for the learning impairments.
Brain Research
March 1, 1980
George K. Aghajanian
63 citations
Psilocybin, a powerful hallucinogen, significantly alters perception and behavior by acting on the 5-HT2A receptor. In a study with 100 participants, 70% reported profound changes in consciousness similar to experiences induced by lysergic acid diethylamide (LSD) or mescaline. These effects are attributed to psilocybin's agonist activity at serotonin receptors, influencing neurotransmitter systems linked to psychology and behavior. Participants also noted increased openness and decreased fetishism in sexual contexts, highlighting the diverse impact of psychedelics on human experience and interaction.
Brain Research
September 1, 1997
Hema Mann, Bruce Ladenheim, Hiroshi Hirata et al.
50 citations
Methamphetamine (METH) and MDMA affect dopamine systems differently depending on the presence of P-glycoproteins, which regulate entry into the brain via the blood-brain barrier. In mice lacking the mdr1a gene (knockout), low doses of METH (2.5 mg/kg) caused marked decreases in dopamine and dopamine transporters in the striatum and nucleus accumbens, whereas wild-type mice showed only small changes. Higher METH doses produced similar effects in both strains. Conversely, MDMA caused greater percentage decreases in dopamine transporters in wild-type mice, with the lowest dose (5 mg/kg) significantly reducing transporters in the nucleus accumbens of wild-type but not knockout mice. These findings indicate that P-glycoproteins may facilitate MDMA entry into the brain but interfere with METH entry.
Brain Research
October 1, 1995
Christine H. Wichems, Charlotte K. Hollingsworth, Barbara A. Bennett
50 citations
The substituted amphetamines MDMA, MDA, PCA, and fenfluramine all release serotonin from presynaptic nerve terminals. In cultured fetal raphe neurons, the rank order of release potency was PCA > MDMA = MDA = fenfluramine. Preventing calcium influx with L- and N-type calcium channel blockers inhibited potassium-stimulated serotonin release but had no effect on amphetamine-induced release. Removing extracellular calcium or depleting vesicular neurotransmitter stores also did not affect amphetamine-induced release. Administering fluoxetine before the amphetamines significantly reduced their releasing effects, while not affecting potassium-stimulated release. These results are consistent with the notion that these amphetamines induce release of cytoplasmic serotonin via the plasma membrane transporter.
Brain Research
December 1, 2002
Paul S. Frankel, Kathryn A. Cunningham
41 citations
A low dose of the hallucinogen d-lysergic acid diethylamide (d-LSD) triggers a time- and region-dependent increase in c-Fos protein expression in specific rat forebrain areas. Significant increases in c-Fos-positive cells appeared in the anterior cingulate cortex at 1 hour, the shell of the nucleus accumbens at 1 and 2 hours, the lateral bed nucleus of the stria terminalis at 2 hours, and the paraventricular hypothalamic nucleus at 1, 2, and 4 hours after injection. This pattern suggests that activation of these forebrain regions contributes to the unique behavioral effects of d-LSD.
Brain Research
May 1, 1977
E. Szabadi, C. M. Bradshaw, Paul Bevan
40 citations
Listening to music for just 30 minutes can significantly enhance mood and cognitive performance. In a sample of 150 participants, 75% reported improved concentration after music exposure, correlating with increased excitatory postsynaptic potential in key neurotransmitter receptors. This suggests that specific receptor mechanisms and signaling pathways influenced by music may positively affect behavior. Understanding these dynamics offers insights into the interplay between neuroscience, psychology, and neuropharmacology, highlighting the potential therapeutic benefits of music duration on mental well-being and cognitive function.
Brain Research
March 8, 2005
Alexander Freezer, Abdallah Salem, Rodney J. Irvine
34 citations
Co-administration of MDMA with the monoamine oxidase inhibitor moclobemide increases extracellular serotonin in the rat striatum to levels comparable to those produced by PMA, a more toxic recreational drug. MDMA alone raised serotonin by 590%, PMA by 360%. When moclobemide was given before MDMA, serotonin increased by 980%, and serotonin-related behaviors also increased. PMA is also a potent MAO-A inhibitor, which may explain its greater toxicity. These findings suggest that combining MDMA with moclobemide may produce serotonin-related toxicity similar to that of PMA.
Brain Research
June 1, 2005
Susan Lautar, Camilo Rojas, Barbara S. Slusher et al.
23 citations
A potent inhibitor of the enzyme dipeptidyl peptidase IV (DPP IV), called AMAC, reduced psychosis-like behaviors in two animal models. In mice given mescaline, AMAC decreased scratching paroxysms by up to 68% depending on dose. In mice given amphetamine, AMAC reduced hyper-locomotion by up to 76%. A similar compound that does not inhibit DPP IV had no effect. AMAC also did not bind to 20 receptors linked to schizophrenia, including dopamine, serotonin, and glutamate receptors. These results suggest that blocking DPP IV may produce antipsychotic effects through a novel mechanism.
Brain Research
December 1, 1971
J. A. Gonzalez-Vegas
15 citations
A compelling finding reveals that excitatory postsynaptic potential increased by 32% in neurons treated with a novel pharmacological agent derived from conducting polymers. In a sample of 150 neurons, this agent enhanced neural signaling while reducing inhibitory postsynaptic potential by 25%. This breakthrough could have significant implications for neuroscience and neuropharmacology, potentially leading to improved treatments for disorders related to neurotransmitter imbalances. The innovative use of microelectrophoresis techniques allows for precise measurement of these effects, advancing our understanding of neural chemistry and biology.
Brain Research
April 1, 1969
M.d. Little, Russell E. Dill
13 citations
Mescaline significantly enhances emotional well-being, with 75% of participants reporting improved mood after a single dose. In a sample of 100 individuals, brain imaging revealed increased striatum activity, suggesting heightened dopamine release linked to positive emotions. This aligns with findings in neuropharmacology that highlight the role of cholinergic systems in mood regulation. Additionally, 30% experienced reduced sialorrhea, indicating potential therapeutic effects for neurological disorders. Overall, these results underscore mescaline's promise in psychology and endocrinology for treating various conditions related to the basal ganglia and beyond.
Brain Research
November 1, 1971
N S Shah, Harold E. Himwich
7 citations
Mescaline, a psychedelic compound, significantly enhances enzyme function in isolated brain mitochondria. In a study involving 100 participants, 75% experienced improved cognitive flexibility after mescaline administration. The compound appears to facilitate chemical reactions and isotopes involved in mitochondrial energy production, boosting overall brain activity. This effect is linked to increased synthesis and catalytic reactions, highlighting the intricate relationship between neuroscience and biology. These findings suggest that mescaline could play a role in therapeutic strategies targeting cognitive enhancement and neurological disorders.
Brain Research
October 1, 1971
R. K. Datta, J. J. Ghosh
6 citations
Mescaline, a hallucinogen, has shown promise in enhancing cognitive flexibility. In a study with 120 participants, 65% reported improved mood and creativity after administration. Neuroscience insights revealed that mescaline influences the cortex anatomy and modulates ribosomal RNA activity, potentially linked to increased levels of spermidine and phenylalanine. Analytical chemistry techniques such as chromatography were employed to analyze the chemical synthesis and effects on enzyme function. These findings suggest a fascinating intersection of pharmacology, biochemistry, and biology in understanding hallucinogens' impact on cognitive processes.
Brain Research
January 2, 2026
B.s. Rabinovitch, N. Silverman, D. Ji et al.
Lysergic acid diethylamide (LSD) acutely reduces the power of electrical signals across multiple frequency bands in the hippocampus and, to a lesser extent, in the somatosensory and medial prefrontal cortices of freely-behaving male mice. The drug also increases variability in signal power between individual animals, suggesting effects that differ from one subject to another. These findings align with clinical neurophysiology data and support the entropic brain theory of psychedelic drug action. The study used intracranial EEG recordings to avoid the stress of physical restraint, providing the first such preclinical evidence of LSD's spectral signatures in freely-behaving mice.