Pyramidal neurons in layer 5 of the cerebral cortex are involved in learning and memory and have complex connections with other neurons through a very large array of dendrites. These dendrites can switch between long term depression and long term potentiation depending on global summation of various inputs. The plasticity of the input into pyramidal neurons ...
RationaleMany studies have reported deficits of mismatch negativity (MMN) in schizophrenic patients. Pharmacological challenges with hallucinogens in healthy humans are used as models for psychotic states. Previous studies reported a significant reduction of MMN after ketamine (N-methyl-D-aspartate acid [NMDA] antagonist model) but not after psilocybin (5HT2...
Aberrations in brain serotonin (5-HT) neurotransmission have been implicated in psychiatric disorders including anxiety, depression and deficits in learning and memory. Many of these disorders are treated with drugs which promote the availability of 5-HT in the synapse. Selective serotonin uptake inhibitors (SSRIs) are known to stimulate the production of ne...
RationaleBinocular rivalry occurs when different images are simultaneously presented to each eye. During continual viewing of this stimulus, the observer will experience repeated switches between visual awareness of the two images. Previous studies have suggested that a slow rate of perceptual switching may be associated with clinical and drug-induced psycho...
N,N-dipropyltryptamine (DPT) is a synthetic tryptamine hallucinogen which has been used psychotherapeutically in humans, but has been studied preclinically only rarely. In the present studies, DPT was tested in a drug-elicited head-twitch assay in mice, and in rats trained to discriminate lysergic acid diethylamide (LSD), N,N-dimethyl-4-phosphoryloxytryptami...
Although psilocybin has been trained in the rat as a discriminative stimulus, little is known of the pharmacological receptors essential for stimulus control. In the present investigation rats were trained with psilocybin and tests were then conducted employing a series of other hallucinogens and presumed antagonists. An intermediate degree of antagonism of ...
Increasing evidence suggests a link between attention, working memory, serotonin (5-HT), and prefrontal cortex activity. In an attempt to tease out the relationship between these elements, this study tested the effects of the hallucinogenic mixed 5-HT1A/2A receptor agonist psilocybin alone and after pretreatment with the 5-HT2A antagonist ketanserin. Eight h...
Pharmacological challenges with hallucinogens are used as models for psychosis in experimental research. The state induced by glutamate antagonists such as phencyclidine (PCP) is often considered as a more appropriate model of psychosis than the state induced by serotonergic hallucinogens such as lysergic acid (LSD), psilocybin and dimethyltryptamine (DMT). ...
Previously the NMDA (N-methyl-D-aspartate) receptor (NMDAR) antagonist ketamine was shown to disrupt generation of the auditory event-related potential (ERP) mismatch negativity (MMN) and the performance of an 'AX'-type continuous performance test (AX-CPT)--measures of auditory and visual context-dependent information processing--in a similar manner as obser...
BackgroundPrevious studies indicate that mismatch negativity (MMN)-a preattentive auditory event-related potential (ERP)-depends on NMDA receptor (NMDAR) functioning. To explore if the strength of MMN generation reflects the functional condition of the NMDAR system in healthy volunteers, we analyzed correlations between MMN recorded before drug administratio...
Increasing evidence from neuroimaging and behavioral studies suggests that functional disturbances within cortico-striato-thalamic pathways are critical to psychotic symptom formation in drug-induced and possibly also naturally occurring psychoses. Recent basic and clinical research with psychotomimetic drugs, such as the N-methyl-D-aspartate (NMDA) glutamat...
The neurotropic effect of Psilocybe cubensis (Earle) Sing, dried biomass and fruiting bodies containing the indole hallucinogens psilocybin and psilocine on spike activity of pyramidal neurons from the rat hippocampal CAl region slices has been studied. Extracellularly responses of 50 neurons were recorded, 34 during the application of biomass extract (BME) ...
The enantiomers of 3-(N-methylpyrrolidin-2-ylmethyl)-5-methoxyindole, 1, and 3-(N-methylpyrrolidin-2-ylmethyl)-4-hydoxyindole, 3, were prepared using an asymmetric synthesis that employed (+)- or (-)-proline. A new approach was developed that had certain advantages over the synthesis originally reported for the isomers of 1. (+/-)-3-(N-Methylpyrrolidin-3-yl)...
Psilocybin, an indoleamine hallucinogen, produces a psychosis-like syndrome in humans that resembles first episodes of schizophrenia. In healthy human volunteers, the psychotomimetic effects of psilocybin were blocked dose-dependently by the serotonin-2A antagonist ketanserin or the atypical antipsychotic risperidone, but were increased by the dopamine antag...
Pigeons (N=4) were trained to discriminate between the effects induced by intramuscular (IM) injections of d-LSD and saline using a discrete-trial discrimination paradigm (choice between left and right hand key) in a conventional operant box. The solutions were administered IM15 min prior to the sessions. A FR15 schedule was in operation to produce food. Whi...
Two aspects of the complexities of the mode of action of drugs are described. One is the criteria and pitfalls of defining the interaction with specific receptors. The other is the need to consider each of the pharmacological effects of a drug as a concatenation of receptor events, because it has become clear that each drug may have substantial affinity for ...
