3,4-Methylenedioxymethamphetamine (MDMA), an important recreational psychostimulant drug, was examined for its ability to alter visuo-spatial learning and synaptic plasticity. Young rats received MDMA (0.2 and 2mg/kg s.c.) twice per day for 6 days while their visuo-spatial learning was tested using the Morris Water Maze. After this, animals were sacrificed and LTP induced in hippocampal slices....
The iboga alkaloid congener, 18-methoxycoronaridine (18-MC), decreases self-administration of multiple drugs of abuse. Here, in a biased procedure, we investigated whether 18-MC would have a similar effect on the acquisition, expression and reinstatement of a cocaine conditioned place preference (CPP) in male Sprague-Dawley rats. While 18-MC attenuated acquisition of a cocaine CPP, it had no...
Boost up gamma-band neuronal oscillations have been interpreted as a correlate of pertinent stimulus awareness. The validity of this observation-based conclusion can be rigorously tested if the basic methodological rule of investigating neural correlates of consciousness (NCC) is followed: the varying contents of consciousness should be contrasted with invariant stimulation. We asked whether...
Locomotor sensitization induced by the dopamine agonist quinpirole can be potentiated by co-treatment with the synthetic kappa opioid agonist U69593. The identification of salvinorin A, an active component of the psychotropic sage Salvia divinorum, as a structurally different agonist of kappa-opioid receptors raised the question of whether this compound would similarly potentiate sensitization...
Neuroscience LettersAugust 22, 2008Shanker Jha, Rajeev Rajendran, Kimberly A Fernandes et al.
Adult hippocampal neurogenesis is reported to be a target of antidepressants, drugs of abuse and animal models of depression, suggesting a role for this form of structural plasticity in psychopathology. Serotonergic neurotransmission, which is implicated in several psychiatric diseases, has been reported to regulate adult hippocampal neurogenesis. Amongst the serotonergic receptors, the...
Mystical experiences relate to a fundamental dimension of human existence. These experiences, which are characterized by a sense of union with God, are commonly reported across all cultures. To date, no electroencephalography (EEG) study has been conducted to identify the neuroelectrical correlates of such experiences. The main objective of this study was to measure EEG spectral power and...
Action of a hallucinogenic substance, psilocybin, on internal time representation was investigated in two double-blind, placebo-controlled studies: Experiment 1 with 12 subjects and graded doses, and Experiment 2 with 9 subjects and a very low dose. The task consisted in repeated reproductions of time intervals in the range from 1.5 to 5s. The effects were assessed by parameter kappa of the...
Delta(9)-tetrahydrocannabinol, the main psychoactive ingredient in marijuana, activates specific cannabinoid (CB) receptors to exert complex actions on modulatory neurotransmitters involved in attention and cognition. Previous research has demonstrated that systemic administration of the synthetic cannabinoid agonist, WIN 55,212-2, increases norepinephrine efflux in the frontal cortex. The...
This study investigated differences in brain activation during meditation between meditators and non-meditators. Fifteen Vipassana meditators (mean practice: 7.9 years, 2h daily) and fifteen non-meditators, matched for sex, age, education, and handedness, participated in a block-design fMRI study that included mindfulness of breathing and mental arithmetic conditions. For the meditation...
Neuroscience LettersNovember 20, 2006Duncan Ryan, Alison J Drysdale, Roger G Pertwee et al.
We have shown previously that the plant cannabinoid cannabidiol (CBD) elevates intracellular calcium levels in both cultured hippocampal neurones and glia. Here, we investigated whether the main psychotropic constituent of cannabis, Delta(9)-tetrahydrocannabinol (THC) alone or in combination with other cannabis constituents can cause similar responses, and whether THC affects the responses...
The main goal of this functional magnetic resonance imaging (fMRI) study was to identify the neural correlates of a mystical experience. The brain activity of Carmelite nuns was measured while they were subjectively in a state of union with God. This state was associated with significant loci of activation in the right medial orbitofrontal cortex, right middle temporal cortex, right inferior...
The subiculum plays a key role in processing neuronal information from the hippocampus to different cortical and subcortical brain regions. The subicular projections to the nucleus accumbens and the prefrontal cortex have received increasing attention, as alterations of their activity seem to be involved in schizophrenia. Phencyclidine and other non-competitive antagonists of NMDA receptors...
Transcranial magnetic stimulation (TMS) with weak (micro Tesla) complex waveform fields have been claimed to evoke the sensed presence of a sentient being in up to 80% in the general population. These findings have had a questionable neurophysiological foundation as the fields are approximately six orders of magnitude weaker than ordinary TMS fields. Also, no independent replication has been...
3,4-methylenedioxymethamphetamine (MDMA, ecstasy) has been shown to induce long-term deficits in serotonergic function in animal models. Several studies have suggested that dopamine (DA) uptake into serotonin (5-HT) terminals by the 5-HT reuptake transporter (SERT) and subsequent deamination by monoamine oxidase-B (MAO-B) leads to the formation of hydrogen peroxide and may be major contributors...
MDMA (3,4 Methylenedioxy-methamphetamine) binds and blocks the presynaptic serotonin reuptake transporters and postsynaptic serotonin 5-HT2A receptors, with highest affinity for the first. Whether 5-HT2A receptor density decreases due to MDMA's direct effect on postsynaptic serotonin receptors is at present not known. This study analyzes whether direct stimulation of the postsynaptic 5-HT2A...
Neuroscience LettersSeptember 27, 2002Werner J Schmidt, Andreas Mayerhofer, Anja Meyer et al.
Parkinson's disease is due to a dopamine deficiency caused by the degeneration of midbrain dopamine neurons. Current therapies are aimed to substitute dopamine or to directly stimulate postsynaptic dopamine receptors. However, not all patients profit from current therapies to the same extent, even serious side effects such as dyskinesias are complicating the therapy. Therefore, there is still a...
Neuroscience LettersSeptember 27, 2002Anja Meyer, Andreas Mayerhofer, Karl‐artur Kovar et al.
3,4-methylenedioxy-methylamphetamine (MDMA) ('Ecstasy') and its analogue 3,4-methylenedioxy-methylamphetamine (MDE) ('Eve') are well known illicit street drugs mainly abused by young people. In spite of the actual research going on, the classification of their abuse potential remains unclear. Since secondary reinforcers are the main factors responsible for craving and relapse, the aim of our...
Phencyclidine (PCP) is known to be an inhibitor of serotonin (5-HT) uptake and to increase serotonergic activity. The development of tolerance to serotonergic stereotyped behaviors induced by repeated PCP treatment and changes of 5-HT transporters were examined. Backpedalling was significantly reduced in frequency following 14 days PCP treatment (7.5 mg/kg per day). Furthermore, repeated PCP...
The effects of phencyclidine (PCP) and its metabolites on serotonin (5-hydroxytryptamine, 5-HT) receptors were studied. PCP and its metabolites inhibited the uptake of [3H]5-HT and the binding of [3H]paroxetine in rat brain, while they failed to inhibit either [3H]5-HT binding to 5-HT1 receptors or [3H]ketanserin binding to 5-HT2 receptors. The trans-isomer of...
The analgesic, subjective, and psychomotor effects of 0, 10, 20, 30, and 40% nitrous oxide in oxygen were studied in 10 volunteers to determine if acute tolerance developed differentially to these variables. In this prospective, randomized, crossover, double-blind study, volunteers inhaled either placebo (100% oxygen) or one of the aforementioned doses of nitrous oxide for 120 min. During this...
The putative anti-addiction alkaloid ibogaine and its principal metabolite 12-hydroxyibogamine appear to act at the (+)-5 methyl-10,11,dihydro-5H- dibenzo[a,d]cycloheten-5-10-imine maleate (MK-801) binding site in the N-methyl-D-aspartate (NMDA)-receptor cation channel. This conclusion is based on findings that both compounds competitively displaced specific [3H]MK-801 binding to membranes from...
Although several beta-carboline alkaloids display hallucinogenic properties in humans, their mechanism of action remains unclear. To ascertain their influence on central dopaminergic transmission, in this study we investigated the facilitating effect of low doses of various beta-carbolines on L-DOPA (250 mg/kg)-induced stereotypy in mice. Harmaline (0.075, 0.15 and 0.35 mg/kg) and harmine...
The effect of the R(-) and S(+) isomers of 3,4-methylenedioxyamphetamine (MDA) and its N-methyl analog 3,4-methylenedioxymethamphetamine (MDMA) on [3H]inositol monophosphate accumulation was studied in cells expressing either 5-HT2A or 5-HT2C receptors. The isomers of MDA produced a concentration dependent increase in phosphatidyl inositol (PI) hydrolysis at the 5-HT2A receptors, with the R(-)...
The reduction of 5-hydroxytryptamine (5-HT) in rat brain 3 h after administration of 3,4-methylenedioxymethamphetamine (MDMA) was attenuated significantly by coadministration of benzylpiperazine derivatives (p-nitrobenzylpiperazine, p-chlorobenzylpiperazine and 1-piperonylpiperazine), which were weak inhibitors of [3H]5-HT uptake into rat brain synaptosomes. However, the coadministration of...
The effects of a serotonin (5-HT) receptor agonist, 5-methoxy-N,N-dimethyltryptamine (5-MeODMT), on epileptic photosensitivity were studied in the lateral geniculate-kindled cat. 5-MeODMT at 4 mg/kg significantly suppressed photically induced myoclonus, but not paroxysmal EEG activity, at 0.5-1 h after injection. This antiepileptic effect was seen in association with the appearance of...