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At least 19 recordsLinked to original sources
PubMed1975

Plasma creatine phosphokinase levels in rats following lysergic acid diethylamide.

Lysergic acid diethylamide (LSD) injected intraperitoneally or intramuscularly did not increase rat plasma creatine phosphokinase (CPK) activity. LSD did not produce an increase in serum CPK activity in rats kept in a 2 degrees C environment for 2 hrs. LSD also did not potentiate, in rats, the increase in plasma CPK activity produced by restraint at 2 degrees C or 24 degrees C. It is likely that the increases in serum CPK activity previously reported to occur in people who became psychotic following LSD ingestion are a consequence of the psychotic state itself rather than a direct effect of LSD.

Animals↗
PubMed1986

The effects of intracranial administration of hallucinogens on operant behavior in the rat. I. Lysergic acid diethylamide.

Lysergic acid diethylamide (LSD) was infused in one microliter volumes into discrete brain regions of rats trained to press a bar for food reinforcement. The sites were chosen as major areas of the brain 5-hydroxytryptamine (5HT) system: the dorsal and median raphe nuclei, dorsal hippocampus, lateral habenular nuclei, and the prefrontal cortex. Following training in a fixed ratio-40 (FR-40) operant behavior rats were implanted for the lateral habenular nuclei, dorsal hippocampus and the prefrontal cortex. Following recovery from surgery, LSD (8.6 to 86 micrograms) or vehicle was infused immediately before a daily operant session. Infusion of vehicle was inactive. LSD produced a dose-dependent decrease in reinforcements and an increase in 10-sec periods of non-responding (pause intervals). LSD was significantly more potent when infused into the dorsal raphe nucleus than following intracerebroventricular (ICV) administration, whereas LSD was less potent when infused into the median raphe, lateral habenula or dorsal hippocampus. ED50s for increases in pause intervals were 9, 13, 23, 25, and 54 micrograms for infusion into the dorsal raphe, prefrontal cortex, dorsal hippocampus, median raphe, and lateral habenular nuclei, respectively. The ED50 for ICV administration in a previous study was 15 micrograms. The ED50 of LSD placed into the prefrontal cortex did not differ significantly from that of the ICV infusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Unsurmountable antagonism of brain 5-hydroxytryptamine2 receptors by (+)-lysergic acid diethylamide and bromo-lysergic acid diethylamide.

Lysergic acid diethylamide (LSD) and its structural analogue 2-bromo-lysergic acid diethylamide (BOL) act as unsurmountable antagonists of serotonin-elicited contractions in smooth muscle preparations. Two different models, allosteric and kinetic, have been invoked to explain these findings. The present studies investigate the mechanism of antagonism of brain 5-hydroxytryptamine (5HT)2 receptors, utilizing cells transfected with 5HT2 receptor cDNA cloned from rat brain. A proximal cellular response, phosphoinositide hydrolysis, was examined in order to minimize possible postreceptor effects. Even though LSD behaved as a partial agonist and BOL as a pure antagonist, both drugs blocked the effect of serotonin in an unsurmountable manner, i.e., increasing concentrations of serotonin could not overcome the blocking effect of LSD or BOL. Radioligand binding studies showed that preincubation of membranes with either LSD or BOL reduced the density of [3H]ketanserin binding sites, suggesting that the drugs bind tightly to the 5HT2 receptor and are not displaced during the binding assay. Two additional experiments supported this hypothesis. First, the off-rate of [3H] LSD was slow (20 min), relative to that of [3H]ketanserin (approximately 4 min). Second, when the length of incubation with [3H]ketanserin was increased to 60 min, the LSD-induced decrease in Bmax was essentially eliminated. The possibility that LSD and BOL decrease [3H]ketanserin binding by interacting with an allosteric site was rejected, because neither drug altered the rate of dissociation of [3H]ketanserin. The most parsimonious interpretation of these results is that unsurmountable antagonism reflects prolonged occupancy of the receptor by slowly reversible antagonists.

3T3 Cells↗
PubMed1977

Antagonism of histamine-activated adenylate cyclase in brain by D-lysergic acid diethylamide.

D-Lysergic acid diethylamide and D-2-bromolysergic acid diethylamide are competitive antagonists of the histamine activation of adenylate cyclase [ATP pyrophosphate-lyase (cyclizing); E.C. 4.6.1.1] in broken cell preparations of the hippocampus and cortex of guinea pig brain. The adenylate cyclase is linked to the histamine H2-receptor. Both D-lysergic acid diethylamide and D-2-bromolysergic acid diethylamide show topological congruency with potent H2-antagonists. D-2-Bromolysergic acid diethylamide is 10 times more potent as an H2-antagonist than cimetidine, which has been the most potent H2-antagonist reported, and D-lysergic acid diethylamide is about equipotent to cimetidine. Blockade of H2-receptors could contribute to the behavioral effects of D-2-bromolysergic acid diethylamide and D-lysergic acid diethylamide.

Adenylyl Cyclases↗
PubMed1979

Distortions of vision and pain: two functional facets of D-lysergic acid diethylamide.

D-lysergic acid diethylamide (LSD) produces distortions of visual perception and analgesia. Evidence is advanced from a functional standpoint that the observed visual effects result from an attenuation of light-evoked input to the dorsal lateral geniculate nucleus (LGN) from the purely centripetal pathways of the retina. More slowly responding visual afferents or those with more complex receptive fields seem to be affected most. LSD analgesia, accompanied by severe psychotic symptoms, appears to result from drug actions on a centrifugally controlled pain system involving neurons of the midbrain raphe.

Animals↗
PubMed1975

Ocular effects of diacetyl morphine and lysergic acid diethylamide in rabbit.

Intravenous lysergic acid diethylamide (LSD) given to rabbits in doses from 1 to 100 mug per kilogram of body weight produced a dose-related increase in intraocular pressure and outflow facility. Minor changes in systemic blood pressure were observed, but respiration rate was accelerated, and mydriasis became pronounced at higher doses. Diacetyl morphine (heroin) was given intravenously in doses from 0.1 to 2 mg. per kilogram of body weight. A dose-related decrease in intraocular pressure and an increase in outflow facility was found. A dose-related miosis was observed and at higher doses respiration became markedly depressed. Neither drug alters the permeability of the isolated ciliary epithelium. Both drugs appear to increase capillary blood pressure and, hence, aqueous humor inflow to cause the intraocular pressure to be maintained at approximately normal levels in face of increases in outflow facility of 50 per cent.

Anesthesia, Intravenous↗
PubMed1979

Fate of mRNA following disaggregation of brain polysomes after administration of (+)-lysergic acid diethylamide in vivo.

Intravenous injection of (+)-lysergic acid diethylamide into young rabbits induced a transient brain-specific disaggregation of polysomes to monosomes. Investigation of the fate of mRNA revealed that brain poly(A+)mRNA was conserved. In particular, mRNA coding for brain-specific S100 protein was not degraded, nor was it released into free ribonucleoprotein particles. Following the (+)-lysergic acid diethylamide-induced disaggregation of polysomes, mRNA shifted from polysomes and accumulated on monosomes. Formation of a blocked monosome complex, which contained intact mRNA and 40-S plus 60-S ribosomal subunits but lacked nascent peptide chains, suggested that (+)-lysergic acid diethylamide inhibited brain protein synthesis at a specific stage of late initiation or early elongation.

Animals↗
PubMed1988

Autoradiographic localization and characterization of [125I]lysergic acid diethylamide binding to serotonin receptors in Aplysia.

The sensitive serotonergic radioligand 2-[125I]lysergic acid diethylamide was used to study the distribution and pharmacological binding properties of serotonin receptors in Aplysia californica. The high specific activity of this radioligand allowed us to develop a methodology for the investigation of receptor binding properties and receptor distribution in a single ganglion. [125I]Lysergic acid diethylamide labels a population of high-affinity serotonergic sites (Kd = 0.41 nM) in Aplysia ganglia whose regional distribution matches that expected from previous electrophysiological and immunohistochemical studies. The properties of [125I]lysergic acid diethylamide binding sites in Aplysia are in general agreement with previous studies on [3H]lysergic acid diethylamide binding in this system but these sites differ from the serotonergic receptor subtypes described in the mammalian brain. Guanine nucleotides were shown to modulate agonist but not antagonist affinity for the [125I]lysergic acid diethylamide binding site in Aplysia, suggesting that this site is coupled to a G-protein. Images of serotonin receptor distribution in the Aplysia nervous system were obtained from autoradiograms of [125I]lysergic acid diethylamide binding. Serotonin receptors in ganglia tissue sections are located primarily within the neuropil. In addition, a subset of neuronal soma are specifically labeled by [125I]lysergic acid diethylamide. These studies indicate that [125I]lysergic acid diethylamide binds to sites in the Aplysia nervous system which display a regional distribution, pharmacological binding properties and evidence of coupling to a G-protein consistent with labeling of a subset of functional serotonin receptors. In addition, the techniques used in this investigation provide a general approach for rapidly characterizing the pharmacological properties and anatomical distribution of receptor binding sites in single invertebrate ganglia. Individual neurons containing these receptor subtypes can be identified by these methods and correlated with physiological responses in the same cell.

Animals↗
PubMed1986

Characterization of a translational inhibitor isolated from rabbit brain following intravenous administration of d-lysergic acid diethylamide.

Intravenous administration of d-lysergic acid diethylamide (LSD) to rabbits results in a transient inhibition of brain protein synthesis in vivo and in vitro. A translational inhibitor that appears in the postribosomal supernatant fraction of cerebral hemispheres following LSD administration was partially purified by gel filtration on Sephadex G-150 and precipitation with 60% ammonium sulfate. This inhibitor, which was proteinaceous, reduced the translational capacity of an initiating cell-free protein synthesis system derived from brain. It also inhibited a messenger RNA-dependent reticulocyte lysate programmed with brain polysomes and a globin-synthesizing reticulocyte lysate system. Addition of the partially purified inhibitor to a brain cell-free protein synthesis system resulted in the decreased formation of ternary complexes as well as 40 and 80S initiation complexes, suggesting that the inhibitor affects an early step in the initiation of protein synthesis in brain.

Animals↗
PubMed1977

Hyperthermic effects of D-lysergic acid diethylamide (LSD) and its derivatives in rabbits and rats.

Several D-lysergic acid diethylamide (LSD) derivatives including metabolites of LSD in animals liver and Streptomyces such as D-lysergic acid ethyl, 2-hydroxyethylamide (LEO), D-lysergic acid ethylamide (LAE), D-norlysergic acid diethylamide (norLSD) and synthetic N6-allyl-D-norlysergic acid diethylamide (allyl-nor LSD) were studied with rabbits and rats. In rabbits, the order of the hyperthermic activities was allyl-norLSD greater than LSD greater than LEO, LAE, nor-LSD, and this order was parallel to that of 5-hydroxytryptamine-like activities of these compounds which was previously studied. However, the order was LAE greater than LSD greater than norLSD IN RATS. The hyperthermic effect of LSD in rabbits was attenuated by methysergide, but not by atropine when these drugs were intraventricularly administered. These results suggest the possibility that the metabolites of LSD contribute to the hyperthermic effect of LSD in rats but not in rabbits, and support the idea that 5-HT receptors are involved in the hyperthermia induced by LSD in rabbits.

5-Hydroxytryptophan↗
PubMed1973

An inhibition of post-ganglionic motor transmission in the mammalian vas deferens by D-lysergic acid diethylamide.

1. Under certain conditions D-lysergic acid diethylamide (LSD), 10(-9)-10(-6) g/ml., exerted an immediate, prolonged and slowly reversible inhibitory effect upon the post-ganglionic motor transmission in desheathed guinea-pig vas deferens preparations.2. The most critical factor influencing this action of LSD appeared to be the train length. With short trains of less than 4 or 5 pulses the twitch inhibition produced by LSD was often total. With longer trains (5-20 pulses), the degree of inhibition declined with increase in train length. These results suggest the existence of two components in the motor response to post-ganglionic stimulation, distinguished by their susceptibility to LSD.3. The inhibition of the LSD-susceptible component was related to the dose of LSD in the range 10(-9)-10(-6) g/ml., reaching a maximum at 0.5-1 x 10(-6) g/ml. The response remnants elicited by trains of more than 5 pulses under these conditions could not be reduced further by a ten- to twenty-fold increase in LSD concentration to 10(-5) g/ml. and were in fact slightly potentiated.4. The inhibition of post-ganglionic motor transmission by LSD was not explicable on the basis of an alpha-adrenoceptor blockade because it was not associated with any reduction in motor responses to noradrenaline.5. The use of propranolol excluded mediation of the LSD-inhibition by beta-adrenoceptors.6. The LSD effect was not due to a non-specific smooth muscle depression because it was not associated with any reduction in motor responses to acetylcholine, ATP or bradykinin.7. The inhibitory effect of LSD on post-ganglionic transmission resembled that of noradrenaline in that it was antagonized by phentolamine; another alpha-adrenoceptor blocking agent, phenoxybenzamine, was less effective than phentolamine in this respect.8. The LSD-inhibition was obtained in preparations taken from reserpinized guinea-pigs.9. The inhibition of motor transmission in the vas deferens by LSD was confirmed in rats, Meriones shawii and rabbits.10. The inhibition of post-ganglionic transmission by LSD was unrelated to its ability to antagonize 5-hydroxytryptamine (5-HT), to which the longitudinal muscle of the guinea-pig vas deferens is insensitive. The more potent 5-HT antagonists, methysergide and BOL 148 were either virtually inactive or considerably weaker than LSD.

Acetylcholine↗
PubMed1975

Lysergic acid diethylamide: effect on histone acetylation in rabbit brain.

Lysergic acid diethylamide increased acetylation of histones in rabbit cerebral hemispheres and midbrain 30 minutes after intravenous administration of the drug at doses of 10 and 100 micrograms per kilogram of body weight. Evidence for the stimulation of acetylation in individual histone bands was obtained after separation by electrophoresis on polyacrylamied gels.

Acetylation↗
PubMed1977

Lysergic acid diethylamide: evidence for stimulation of pituitary dopamine receptors.

Lysergic acid diethylamide (LSD), 0.05 mg/kg and 0.20 mg/kg, significantly decreased plasma prolactin (PRL) levels in male rats. LSD, 0.20 mg/kg, also inhibits the increase in plasma PRL levels produced by chlorpromazine (CPZ), 5 mg/kg, and alpha-methyl-paratyrosine (AMPT), 50 mg/kg, both of which interfere with dopaminergic inhibition of PRL secretion. LSD was more potent than methysergide, a serotonin receptor blocker, in lowering plasma PRL levels and more potent than apomorphine, a known direct acting dopamine agonist, in blocking the increase in plasma PRL produced by quipazine, a 5-HT agonist. These results suggest LSD has potent dopamine agonist properties on the rat pituitary or hypothalamic dopamine receptors which directly or indirectly inhibit PRL secretion.

Animals↗
PubMed1974

Reversal learning enhanced by lysergic acid diethylamide (LSD): concomitant rise in brain 5-hydroxytryptamine levels.

1 Small doses of lysergic acid diethylamide (LSD) (12.5-50 mug/kg) consistently facilitated learning of a brightness discrimination reversal.2 2-Bromo-lysergic acid diethylamide (BOL-148), a structural analogue of LSD, with similar peripheral anti-5-hydroxytrypamine activity but no psychotomimetic properties, had no effect in this learning situation at a similar dose (25 mug/kg).3 LSD, but not BOL-148, caused a small but significant increase in brain 5-hydroxytryptamine levels, but had no effect on the levels of catecholamines in the brain at 25 mug/kg.

Animals↗
PubMed1988

Antagonism of 5-hydroxytryptamine2 receptor-mediated phosphatidylinositol turnover by d-lysergic acid diethylamide.

The interactions of the indolealkylamine hallucinogen d-lysergic acid diethylamide (d-LSD) and two phenalkylamine hallucinogens, 2,5-dimethoxy-4-bromoamphetamine (DOB) and 2,5-dimethoxy-4-iodoamphetamine (DOI), with 5-hydroxytryptamine2 (5-HT2) receptors were analyzed in rat cortex using both radioligand binding techniques and biochemical measurements of phosphatidylinositol (PI) turnover. 5-HT2 binding sites were labeled by [3H]ketanserin. DOB and DOI displayed decreased affinity for 5-HT2 sites in the presence of 10(-4) M GTP, whereas the ability of d-LSD to compete for these sites was not affected by the presence of 10(-4) M GTP. Moreover, the Hill slope of the d-LSD competition curve was unity in both the absence and presence of 10(-4) M GTP. These findings suggest that d-LSD is an antagonist at 5-HT2 receptors. PI turnover studies in rat cortex showed that at 10(-5) M concentrations d-LSD, DOB and DOI display partial agonist activity in comparison to 10(-5) 5-HT. Stimulation of PI turnover by 5-HT, DOB and DOI was inhibited by the 5-HT2 antagonist ketanserin (10(-6) M). The d-LSD PI signal was not affected by the presence of ketanserin. In addition, nanomolar concentrations of d-LSD did not stimulate PI turnover in rat cortex. Moreover, nanomolar concentrations of d-LSD are able to significantly antagonize the stimulatory effect of 10(-5) M 5-HT on PI turnover. These data suggest that d-LSD acts as an antagonist at 5-HT2 receptors in rat cortex. At high concentrations (greater than 1 microM) d-LSD stimulates low-level PI turnover via a non-5-HT2 receptor-mediated mechanism.

DOM 2,5-Dimethoxy-4-Methylamphetamine↗
PubMed1974

Mechanism of lysergic acid diethylamide interference with rabbit antibody biosynthesis.

Lymphoid cells from hyperimmune rabbits producing antibodies to a hapten, incubated in the presence of d-lysergic acid diethylamide, continued to synthesize protein at a normal rate. Isoelectric focusing analysis of the low-molecular-weight protein secreted by the cells incubated with lysergic acid diethylamide indicated two components, with pI's of 4.9 and 5.2. Immune cells not exposed to lysergic acid diethylamide secreted only 7S IgG molecules with an average pI of approximately 7.0.

Animals↗