Studies have implicated the serotonin (5-HT)(7) receptor in physiological and pathophysiological phenomena, including thermoregulation, central control of micturition and locomotion, regulation of circadian rhythm, sleep, and depression. Further, several antidepressant and antipsychotic drugs have high affinity for the 5-HT(7) receptor. We examined the role of 5-HT(7) receptors in a rodent...
Patients with schizophrenia exhibit diminished prepuLse inhibition (PPI) of the acoustic startle reflex and deficits in the attentional moduLation of PPI. Pharmacological challenges with hallucinogens are used as models for psychosis in both humans and animals. RemarkabLy, in contrast to the findings in schizophrenic patients and in animal hallucinogen modeLs of psychosis, previous studies with...
Schizophrenia patients exhibit impairments in prepulse inhibition (PPI) of the startle response. Hallucinogenic 5-HT(2A) receptor agonists are used for animal models of schizophrenia because they mimic some symptoms of schizophrenia in humans and induce PPI deficits in animals. Nevertheless, one report indicates that the 5-HT(2A) receptor agonist psilocybin increases PPI in healthy humans....
The hallucinogen 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) is structurally similar to other indoleamine hallucinogens such as LSD. The present study examined the effects of 5-MeO-DMT in rats using the Behavioral Pattern Monitor (BPM), which enables analyses of patterns of locomotor activity and exploration, and the prepulse inhibition of startle (PPI) paradigm. A series of interaction...
3,4-Methylenedioxymethamphetamine (MDMA, ecstasy) is neurotoxic upon central serotonin systems in experimental animals and probably also in humans. Serotonin is involved in the habituation, sensitization and prepulse inhibition (PPI) of the startle reflex. To study the plasticity of startle reflex in currently abstinent MDMA users. Electromyographic responses to acoustic startle stimuli (pulse...
Since the mid 1990s, MDMA has been increasingly used as a recreational drug called "Ecstasy" by young people in Europe and the United States. However, despite the widespread recreational use of Ecstasy, systematic data on the psychological and neurobiological effects of MDMA have been scant. To further our understanding of the mechanism of action of MDMA, the authors conducted several studies...
Since being classified as a Schedule I controlled substance, MDMA (3,4-methylenedioxy-N-methylamphetamine; "ecstasy") has been the subject of controversy regarding its potential therapeutic usage, increased use by young people in the "Rave" culture, and issues of potential neurotoxicity. This review article summarizes much of the animal and human studies of the general behavioral effects of...
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) glutamate receptor antagonist, ketamine, and...
Prepulse inhibition (PPI) is the normal reduction of the startle response which occurs when an abrupt startling stimulus is preceded by a weak pre-stimulus and is decreased in several neuropsychiatric disorders. The role of the serotonin 1B (5-HT(1B)) receptor in modulating PPI was investigated using 5-HT-releasing agents in wild-type (WT) and 5-HT1B knockout (1BKO) mice. Whether the...
NMDA antagonists and dopamine (DA) agonists produce neuropathological and/or behavioral changes in rats that may model specific abnormalities in schizophrenia patients. In adult rats, NMDA antagonists and DA agonists disrupt sensorimotor gating-measured by prepulse inhibition (PPI)-modeling PPI deficits in schizophrenia patients. In addition, high doses of NMDA antagonists produce limbic system...
Phencyclidine (PCP), a non-competitive NMDA antagonist with actions at multiple other central nervous system receptors, can cause both acute and lasting psychoses in humans, and has also been used in cross-species models of psychosis. Acute exposure to PCP in rats produces behavioral changes, including a loss of prepulse inhibition (PPI) of the startle reflex, which parallels the loss of PPI...
NeuronMarch 1, 1999R. Grailhe, C. Waeber, S. Dulawa et al.
In order to determine the distribution and function of the 5-HT5A serotonin receptor subtype, we generated knockout mice lacking the 5-HT5A gene. Comparative autoradiography studies of brains of wild-type (wt) and 5-HT5A knockout (5A-KO) mice revealed the existence of binding sites with high affinity for [125I]LSD that correspond to 5-HT5A receptors and that are concentrated in the olfactory...
Schizophrenic patients exhibit deficits in indices of sensorimotor gating, such as habituation and prepulse inhibition (PPI) of the startle reflex. Hallucinogenic drug-induced states are putative models for the early and acute stages of schizophrenic and schizophrenia-spectrum disorders. Hallucinogenic drugs have been shown to disrupt PPI and/or retard habituation of the startle reflex in...
Like hallucinogenic 5-HT2 agonists, LSD (d-lysergic acid diethylamide) produces characteristic decreases in locomotor activity and investigatory behaviors of rats tested in a novel environment. Because LSD is an agonist at both 5-HT1A and 5-HT2 receptors, however, the respective influences of these different receptors in the behavioral effects of LSD remain unclear. In particular, the paucity...
Several reports have speculated that the tryptamine-derived drug alpha-ethyltryptamine (AET) may have effects similar to those of the amphetamine-derived drug 3,4-methylenedioxymethamphetamine (MDMA). Indeed, the US Drug Enforcement Administration has recently placed AET on the Schedule I list because of its putative similarity to MDMA. The Behavioral Pattern Monitor, which quantifies locomotor...
Previous studies indicate that 3,4-methylenedioxymethamphetamine (MDMA) produces locomotor hyperactivity in rats by increasing the presynaptic release of serotonin (5-HT). Interactions between MDMA and 5-HT receptor antagonists suggest that the activating effects of MDMA are mediated via 5-HT1-like receptors. In order to assess the contribution of particular 5-HT receptor subtypes to the...
This study examined the behavioral effects in rats of intracerebral administration of S(+)-3,4-methylenedioxymethamphetamine (S-MDMA) using an automated holeboard and open-field apparatus. Administration of S-MDMA into the nucleus accumbens septi produced locomotor hyperactivity. Although the stimulant effects of S-MDMA administered systemically are antagonized by fluoxetine pretreatment, the...
Derivatives of amphetamine are potent releasers of both dopamine (DA) and serotonin (5-HT), but the relative contributions of DA and 5-HT release to the behavioral effects of these drugs have not been established. Previously, S-(+)3,4-methylenedioxymethamphetamine (S-(+)MDMA) was found to produce locomotor hyperactivity in rats which was dependent on 5-HT release. The present study found that...
Rats tested for 1 h in the Behavioral Pattern Monitor (BPM) after injection of the mixed serotonergic agonist d-lysergic acid diethylamide (LSD) exhibit a behavioral profile similar to that produced by various hallucinogenic 5HT-2 agonists. The characteristic effects of the hallucinogens include suppression of locomotor and exploratory behavior and a preferential decrease in entries into the...
Methylenedioxymethamphetamine (MDMA) is a phenylethylamine with novel mood-altering properties in humans. MDMA shares the dopamine-releasing properties of amphetamine but has been found to be a more potent releaser of serotonin (5-HT). The present study undertook to determine the relative roles of dopamine and 5-HT release in MDMA-induced locomotor hyperactivity. S-(+)MDMA produced...
In rats tested during their first exposure to a Behavioral Pattern Monitor chamber, acute injections of the 5HT-2 agonists mescaline, quipazine, 2,5-dimethoxy-4-iodoamphetamine (DOI), 2,5-dimethoxy-4-methylamphetamine (DOM), or 2,5-dimethoxy-4-ethylamphetamine (DOET) produced an inhibition of locomotor and investigatory behavior during the first 30 min of the test session. This suppression of...
Behavioral profiles composed of both locomotor activity and investigatory behavior were established for the 5HT-1A agonists 8OHDPAT, buspirone, gepirone, and ipsapirone using rats tested in a Behavioral Pattern Monitor. Typically these compounds dose-relatedly decreased horizontal locomotion and investigatory activity during the first half of the 1-h test session. Time-course studies revealed...
The effects of methylenedioxymethamphetamine (0.63-10.0 mg/kg) and N-ethyl-methylenedioxyamphetamine (1.0-10.0 mg/kg) on locomotor and investigatory responses of rats were measured in the Behavioral Pattern Monitor system, a system designed to measure both the quantity and quality of behavioral activity. Horizontal locomotion was increased considerably by these compounds in a dose-related...
A previously proposed animal model of lysergic acid diethylamide's (LSD) effects in humans was tested for its applicability to other hallucinogens, 2,5-dimethoxy-4-methyl amphetamine (DOM) and N,N-dimethyltryptamine (DMT). Both "free" and "forced" exploration tests in a behavioral pattern monitor were used to determine the effects of these hallucinogens on the normal tendencies of rats to avoid...
A free exploration test was used to examine the effects of LSD on investigatory responding and locomotor activity in a novel environment. Rats were injected with 20–30 μg/kg LSD or saline prior to being placed in a home cage. After 10 min, a door was opened permitting entry into a larger holeboard chamber where crossovers, rearings, hole pokes, and routes of locomotion were monitored. When...