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
April 1, 1999
George K. Aghajanian, Gerard J. Marek
379 citations
Serotonin (5-HT) increases spontaneous excitatory postsynaptic currents (EPSCs) in layer V pyramidal cells of the prefrontal cortex via 5-HT2A receptors, a site linked to hallucinogenic and atypical antipsychotic drug action. This effect is Ca2+-dependent and tetrodotoxin-sensitive but does not involve excitatory afferent impulse flow, suggesting an atypical mode of transmitter release. In rat brain slices, the frequency of 5-HT-induced EPSCs is fully supported by Sr2+ in the absence of Ca2+, implicating asynchronous release via the high-affinity Ca2+-sensor synaptotagmin III. The 5-HT2A partial agonist DOI enhances late, nonsynchronous components of evoked EPSCs, blocked by the selective antagonist MDL 100,907. This enhancement of asynchronous EPSCs by a neurotransmitter receptor is novel and may contribute to hallucinogenic effects.
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 19, 1994
S D Glick, M E Kuehne, J Raucci et al.
189 citations
Several iboga alkaloids and the related harmala alkaloid harmaline reduce morphine and cocaine self-administration in rats in a dose-dependent manner (2.5-80 mg/kg) during the hour after treatment. Some alkaloids, including ibogaine, tabernanthine, desethylcoronaridine, and the R-isomers of coronaridine and ibogamine, also decrease intake the following day. In some rats, a single injection or two to three weekly injections produce persistent decreases lasting several days, with R-ibogamine showing the most consistent long-term effects. The study also assessed the tremor-inducing and neurotoxic potential of these compounds and their effects on dopamine levels in brain reward regions.
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
February 7, 1992
D C Deecher, M Teitler, D M Soderlund et al.
143 citations
Ibogaine and related compounds bind to various opioid receptors, with ibogaine showing affinity for kappa-opiate receptors (Ki = 2.08 µM), while harmaline and harmine do not bind to opiate receptors. All tested drugs also affect sodium channels at micromolar concentrations, but neither ibogaine nor harmaline interacts with GABA receptors. The kappa-opioid activity may explain ibogaine's proposed anti-addictive effects, while sodium channel effects could account for the tremor-inducing properties of ibogaine and harmaline.
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
May 6, 1996
S D Glick, M E Kuehne, I M Maisonneuve et al.
118 citations
A novel synthetic compound, 18-methoxycoronaridine (MC), reduces morphine and cocaine self-administration in rats without the tremors and cerebellar toxicity seen with ibogaine. In acute tests, MC decreased drug intake but did not affect bar-press responding for water. In some rats, a single 40 mg/kg dose of MC produced prolonged decreases in morphine or cocaine intake lasting days or weeks. MC showed no tremorigenic effect, and a high dose of 100 mg/kg caused no cerebellar toxicity. Like ibogaine, MC lowered extracellular dopamine levels in the nucleus accumbens. MC appears to be a safer ibogaine-like agent potentially useful for treating addiction.
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
March 13, 1992
I M Maisonneuve, K L Rossman, R W Keller et al.
86 citations
Ibogaine, a compound proposed for treating addiction to opiates and stimulants, produces both immediate and lasting changes in brain dopamine levels. One hour after a single injection, dopamine decreased by 50% while its metabolite HVA increased by 37–100% in the striatum, nucleus accumbens, and prefrontal cortex. Nineteen hours later, another metabolite, DOPAC, was reduced in the nucleus accumbens and striatum, and striatal DOPAC remained low after a week. No significant neurochemical changes were present after one month. Ibogaine pretreatment also reduced the stimulatory effect of morphine on movement when morphine was given 19 hours or a week later, but not after a month. These findings suggest ibogaine's effects on dopamine systems coincide with a sustained dampening of morphine-induced motor activity.
Brain Research
March 27, 1995
S M Pearl, K Herrick-Davis, M Teitler et al.
78 citations
Noribogaine, a suspected metabolite of ibogaine, binds more strongly than ibogaine to all three types of opioid receptors. Ibogaine had highest affinity for kappa receptors, less for mu, and no measurable affinity for delta receptors. Noribogaine showed higher affinity for kappa, mu, and delta receptors, suggesting it is active in the body and may contribute to ibogaine's effects.
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 25, 1996
S D Glick, S M Pearl, J Cai et al.
63 citations
Ibogaine, a natural alkaloid, is claimed to reduce opioid and stimulant addiction for six months after a single dose, though it is eliminated from the body within hours. A metabolite, noribogaine, may explain this prolonged effect. In rats, a 40 mg/kg dose of noribogaine decreased morphine and cocaine self-administration, reduced morphine-induced locomotor stimulation, and lowered dopamine levels in the nucleus accumbens and striatum—effects similar to those of ibogaine at the same dose, but without ibogaine-like tremors. These findings suggest noribogaine mediates ibogaine's anti-addictive properties.
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
October 21, 1996
H H Molinari, I M Maisonneuve, S D Glick
61 citations
High doses of ibogaine (100 mg/kg or repeated doses) cause degeneration of cerebellar Purkinje cells in rats, particularly in lobules 5 and 6, which may lead to motor deficits in the head and upper extremities. In contrast, a lower dose (40 mg/kg) that is effective in reducing morphine and cocaine self-administration produces no more degeneration than saline. The findings suggest that ibogaine's degenerative effects and its anti-addictive properties stem from different mechanisms of action.
Brain Research
January 1, 2025
Leonor Miranda
59 citations
Activating 5HT2A receptors in the anterior cingulate cortex (ACC) with psychedelic drugs reduces anxious preoccupation, obsessional thoughts, and anhedonia while promoting cognitive flexibility and long-lasting mood improvements. This occurs through enhanced AMPA receptor signaling that alters the AMPA-to-NMDA activity ratio, dismantling established neuronal connections and aiding new ones, which benefits fear extinction and reversal learning. Psychedelics also strengthen connectivity from the dorsal ACC and Salience Network to the Default Mode Network and Central Executive Network, improving attentional shifting and anti-anhedonic effects, while reducing the Default Mode Network's inhibitory influence over the Central Executive Network to decrease overevaluation of internal states. Downstream effects include reduced amygdala reactivity to threats and enhanced mesolimbic dopamine, improving anxiety and natural reward experience.
Brain Research
May 1, 1992
I M Maisonneuve, R W Keller, S D Glick
53 citations
Ibogaine, a substance proposed for treating stimulant addiction, was tested in rats. When given 19 hours before D-amphetamine, ibogaine increased the rise in extracellular dopamine in the striatum and nucleus accumbens and enhanced the motor-stimulating effects of D-amphetamine across several doses. These results suggest ibogaine might increase the reinforcing efficacy of D-amphetamine, but because high doses of D-amphetamine can be aversive, the potentiation could also reduce reinforcing efficacy.
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
August 3, 1998
D Wei, I M Maisonneuve, M E Kuehne et al.
48 citations
Ibogaine, its metabolite noribogaine, and the related compound 18-methoxycoronaridine (18-MC) have been claimed to reduce addiction in animal models, but their mechanisms are unclear. In awake female rats, ibogaine caused large increases in extracellular serotonin in the nucleus accumbens (up to 25-fold) and striatum (up to 10-fold), noribogaine produced moderate increases (up to 8-fold and 5-fold), and 18-MC had no effect. These results suggest that the serotonin system may not be essential for anti-addictive effects; ibogaine may both release and block reuptake of serotonin; its hallucinogenic effect may involve serotonin stimulation; and 18-MC likely lacks serotonin transporter affinity and is unlikely to be a hallucinogen.
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.