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At least 973 records · Page 54Linked to original sources
PubMed1985

Involvement of 5-HT2 receptors in the LSD- and L-5-HTP-induced suppression of lordotic behavior in the female rat.

Copulatory behavior in the ovariectomized rat, the lordotic response (L.R.), was induced by estrogen followed by progesterone. L.R. is inhibited by lysergic acid diethylamide (LSD) (greater than or equal to 0.05 mg/kg) and by Levo-5-hydroxytryptophan (L-5-HTP) (greater than or equal to 2.5 mg/kg). The effects of the putative 5-HT antagonists lisuride, metergoline, methysergide, mianserin, cinanserin, cyproheptadine, pirenperone and altanserin on the LSD-induced inhibition of L.R. were tested. Lisuride, metergoline, methysergide and mianserin were found to have no LSD-blocking effect. In contrast, cinanserin, cyproheptadine and pirenperone acted antagonistically to LSD, within a critical dose range. The selective 5-hydroxytryptamine2 (5-HT2) receptor antagonist altanserin effectively prevented the LSD-induced inhibition of L.R., and the doses required (0.05-0.20 mg/kg) indicated a comparatively high antagonistic potency. In addition altanserin (0.2 mg/kg) effectively prevented the lordosis inhibitory effect induced by L-5-HTP (2.5 mg/kg), after pretreatment with pargyline and RO4-4602. It is suggested that the suppression of copulatory behavior caused by LSD and L-5-HTP is mediated by 5-HT2 receptors.

5-Hydroxytryptophan↗
PubMed1983

A characterization of LSD-antagonist effects of pirenperone in the rat.

Rats were trained to discriminate between intraperitoneal injections of 0.16 mg/kg of d-lysergic acid diethylamide (d-LSD) and injections of saline in the two-bar (FR 10) food-reinforced drug discrimination procedure. The gradient for responses to LSD was established following pretreatment with saline or one of five doses of pirenperone. It was found that pretreatment with pirenperone caused a parallel shift to the right of the dose-effect curve of LSD. The magnitude of this shift was related to the dose of pirenperone, 0.006 mg/kg of the drug causing a 2-fold shift. A direct linear plot revealed that the curve fitting the data points passed through the origin, but that it was curvilinear rather than linear. The data did not, therefore, accommodate the requirements for reversible, competitive interaction. This finding is discussed in terms of the mixed agonist/antagonist activity of LSD that may occur at binding sites for 5-HT1 and 5-HT2 in the rat brain.

Animals↗
PubMed1996

Characterisation of human 5-hydroxytryptamine2A and 5-hydroxytryptamine2C receptors expressed in the human neuroblastoma cell line SH-SY5Y: comparative stimulation by hallucinogenic drugs.

Stable transfection of the human neuroblastoma cell line SH-SY5Y with the human 5-hydroxytryptamine2A (5-HT2A) or 5-HT2C receptor cDNA produced cell lines demonstrating ligand affinities that correlated closely with those for the corresponding endogenous receptors in human frontal cortex and choroid plexus, respectively. Stimulation of the recombinant receptors by 5-HT induced phosphoinositide hydrolysis with higher potency but lower efficacy at the 5-HT2C receptor (pEC50 = 7.80 +/- 0.06) compared with the 5-HT2A receptor (pEC50 = 7.30 +/- 0.08). Activation of the 5-HT2A receptor caused a transient fourfold increase in intracellular Ca2+ concentration. Whole-cell recordings of cells clamped at -50 mV demonstrated a small inward current (2 pA) in response to 10 microM 5-HT for both receptors. There were no differences in potency or efficacy of phosphoinositide hydrolysis among four hallucinogenic [d-lysergic acid diethylamide (LSD), 1-(4-iodo-2,5-dimethoxyphenyl)-2-aminopropane (DOI), 5-methoxy-N,N-dimethyltryptamine, and mescaline] and three nonhallucinogenic drugs (m-chlorophenylpiperazine, quipazine, and ergotamine). Comparison of equipotent doses producing 20% of the maximal response induced by 5-HT revealed selective activation of the 5-HT2A receptor by LSD and to a lesser degree by DOI, mescaline, and ergotamine. Quipazine and 5-methoxy-N,N-dimethyltryptamine were relatively nonselective, whereas m-chlorophenylpiperazine selectively activated the 5-HT2C receptor. It is unlikely therefore that hallucinosis is mediated primarily by activity at the 5-HT2C receptor, whereas activity at the 5-HT2A receptor may represent an important but not unique mechanism associated with hallucinogenic drug action.

Adrenergic alpha-Agonists↗
PubMed1983

Interaction of synthetic opioid metenkephalin peptide analogs, Lilly 127623 and FK 33-824 with indole hallucinogens: antagonism of N,N-dimethyltryptamine- and LSD-induced disruption of food-rewarded bar pressing behavior in the rat.

The selected opioid metenkephalin synthetic peptide analogs Lilly (LY) 127623 and FK 33-824 were tested for behavioral dose effects and potential interaction with N,N-dimethyltryptamine (DMT) and lysergic acid diethylamide-25 (LSD) in adult male Holtzman rats trained on a positive reinforcement fixed-ratio 4 (FR-4) behavioral bar pressing schedule, i.e., a reward of 0.01 ml sugar-sweetened evaporated milk was earned on every fourth bar press. DMT (3.2 mg/kg) and LSD (0.1 mg/kg), administered IP following a 0.9% NaCl 15-20-min control pretreatment, disrupted established food-rewarded FR-4 bar pressing in a consistent and reproducible manner. Animals pretreated IP with predetermined behaviorally noneffective doses of LY 127623 (0.01-0.32 mg/kg) and FK 33-824 (0.001-0.01 mg/kg) 15-20 min prior to receiving DMT demonstrated significant antagonism to DMT-induced disruption of FR-4 bar pressing, while doses of 0.10-0.32 mg/kg LY 127623 and 0.00032-0.0032 mg/kg FK 33-824 significantly antagonized LSD-induced behavioral effects.

Animals↗
PubMed1983

Pharmacological evidence for the existence of multiple functional pools of brain serotonin: analysis of brain perfusate from conscious rats.

The serotonin reuptake inhibitor fluoxetine significantly reduced levels of endogenous 5-hydroxyindoleacetic acid (5-HIAA) in brain perfusate of rats implanted with push-pull cannulas. This occurred in conjunction with its suppressant effect upon fixed-ratio operant behavior. Behavior suppressed with the serotonin agonist lysergic acid diethylamide (LSD) occurred in conjunction with a reduction of 5-HIAA only after 5-HIAA was elevated, shortly before, by 5 mg/kg of the serotonin precursor 5-hydroxytryptophan. Our data demonstrate the likely existence of multiple functional pools of serotonin in brain and support the notion that LSD preferentially affects a newly synthesized pool of this transmitter.

5-Hydroxytryptophan↗
PubMed1994

Involvement of 5-HT2C receptors in mediating the discriminative stimulus properties of m-chlorophenylpiperazine (mCPP).

Rats were trained to discriminate the 5-HT receptor agonist m-chlorophenylpiperazine (mCPP; 1 mg/kg) from saline using a two-lever, water-reinforced drug discrimination task. The antidepressant trazodone (1-8 mg/kg), the 5-HT1B/2C receptor agonists 1-(m-trifluoromethylphenyl)piperazine (TFMPP; 0.25-1 mg/kg) and MK 212 (0.125-1 mg/kg), and the mixed 5-HT1A/B receptor agonist RU 24969 (0.25-2 mg/kg) substituted fully for mCPP. The 5-HT2A/2C receptor agonists 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI; 0.25-1 mg/kg) and d-lysergic acid diethylamide (LSD; 0.02-0.08 mg/kg) and the 5-HT releaser fenfluramine (0.5-2 mg/kg) also mimicked mCPP. Agonists selective for the 5-HT1A or 5-HT3 receptor or the 5-HT reuptake site produced saline-lever responding. The ergoline derivative mesulergine (0.5-4 mg/kg) produced a partial agonist/antagonist profile. The 5-HT1/2 receptor antagonist metergoline (0.125-1 mg/kg) completely blocked the mCPP cue whereas the 5-HT2A/2C receptor antagonists ketanserin and LY 53857 as well as all other 5-HT receptor antagonists failed to block the mCPP cue. The dopamine receptor antagonists SCH 23390 and haloperidol were also ineffective mCPP antagonists. Following pretreatment with the 5-HT synthesis inhibitor p-chlorophenylalanine (pCPA; 100 mg/kg/day) for 3 consecutive days, the discriminability of low doses of mCPP increased, whereas the effects of fenfluramine decreased. The present results suggest that the discriminative stimulus effects of mCPP in rats are mediated primarily by postsynaptic 5-HT2C receptors.

Animals↗
PubMed1979

Specificity of serotoninergic inhibition in Limulus lateral eye.

The receptor specificity for synaptically mediated lateral inhibition in Limulus lateral eye retina was studied by structure-activity correlations of the action of the putative indoleaminergic neurotransmitter, serotonin (5-HT), and its isomers and structural analogs, tryptamine (TRYP), 6-hydroxytryptamine (6HT), 5,6-dihydroxytryptamine (5,6-DHT), 5-hydroxydimethyltryptamine (5-HDMT), and 5-hydroxytryptophan (5-HTP). The 5-HT blockers, lysergic acid diethylamide (LSD), bromo-LSD (BOL), and cinanserin, were also tested. The inhibitory action of the indoleaminergic agonists is highly structure-specific. An hydroxyl group in the 5 position of the indole nucleus, sterically unencumbered by hydroxyls in neighboing positions, is essential. In order of decreasing potency, 5-HT, 5-HDMT, and 5-HTP are active agonists; TRYP, 6-HT, and 5,6-DHT are inactive. Configuration and mobility of the side chains of the active agonists also affect the interaction, and these side-chain characteristics correlate with agonist potency. The receptors for inhibitory action and for transmembranal transport in reuptake are different. Both active agonists and inactive analogs appear to be taken up (Adolph and Ehinger, 1975. Cell Tissue Res. 163:1-14). LSD and BOL have bimodal actions: direct inhibition and agonist blockade. These actions may be mediated via low-specificity presynaptic uptake receptor sites rather than highly specific, postsynaptic, agonist receptor sites.

5-Hydroxytryptophan↗
PubMedDate not supplied

Determination of LSD in urine by capillary column gas chromatography and electron impact mass spectrometry.

A procedure for the determination of LSD (lysergic acid diethylamide) in urine at concentrations as low as 0.5 ng/ml is presented. After addition of deuterium-labeled LSD as the internal standard, a rapid n-butyl chloride extraction of LSD from urine at pH 8 is followed by formation of the trimethylsilyl (TMS) derivative by treatment with N,O-bis(trimethylsilyl)trifluoroacetamide. The TMS derivative of LSD is identified and quantified by selected ion monitoring with a fused-silica capillary column and electron impact ionization. The procedure was used to monitor LSD concentrations in urine for eight hours following oral administration of 70.5 micrograms of LSD to two human volunteers. Concentrations of LSD determined by the assay are compared with concentrations determined by two other methods of analysis, a radioimmunoassay and a high-performance liquid chromatographic (HPLC) assay. Data concerning the stability of LSD in urine are also presented.

Chromatography, Gas↗
PubMed1986

Cueing effects of amphetamine and LSD: elicitation by direct microinjection of the drugs into the nucleus accumbens.

Two groups of rats were trained to discriminate either d-amphetamine sulphate (AMPH; 1 mg/kg) or d-lysergic acid diethylamide bitartrate (LSD; 0.16 mg/kg). Microinjection of AMPH into the nucleus accumbens elicited a cueing effect which was similar to that of systemically administered AMPH in AMPH-trained animals (ED50 was 0.24 micrograms). Co-injection of (-)-sulpiride (50 or 100 ng) into the accumbens antagonized the effect of a fixed dose of AMPH (1 microgram) which, alone, produced 76% of the systemic AMPH cue effect. Microinjections of AMPH (1-5 micrograms) into either the anterior dorsomedial or the anterior ventrolateral striatum failed to elicit the cueing effect of AMPH. In LSD-trained animals a dose of 1 microgram LSD injected into the accumbens produced 84% of the systemic cueing effect of LSD. These results suggest that dopamine (DA) receptors in the nucleus accumbens are involved in AMPH discrimination. Furthermore, since both classical and atypical antipsychotic drugs block the AMPH cue, the results provide indirect evidence for involvement of mesolimbic DA in antipsychotic drug action.

Amphetamine↗
PubMed1990

Modulation by drugs of the release of total tritium and 3H-5-HT from rat hypothalamic slices.

The release of total tritium and 3H-5-hydroxytryptamine (5-HT) evoked by electrical stimulation from prelabelled rat hypothalamic slices was studied. Lysergic acid diethylamide (LSD) decreased white methiothepin increased both total tritium and 3H-5-HT overflow. The proportion of total tritium present as 3H-5-HT was equivalent under control conditions and in the presence of methiothepin and slightly increased in the presence of LSD. Whereas the addition of the 5-HT uptake blocker, citalopram, did not modify the evoked release of total tritium, the monoamine oxidase inhibitor, pargyline, decreased it. In the presence of either of these drugs the proportion of 3H-5-HT was increased. In the presence of citalopram, the inhibition by LSD was reduced on both the release of total tritium and of 3H-5-HT. It thus appears that changes in electrically evoked total tritium overflow in general reflect changes in 3H-5-HT release. When uptake inhibitors or monoamine oxidase inhibitors are present in the medium, the situation is, however, more complex and results from experiments measuring only the release of total tritium should be interpreted with caution.

Animals↗
PubMed1981

The role of central serotonergic mechanisms on head-twitch and backward locomotion induced by hallucinogenic drugs.

Head-twitch induced by lysergic acid diethylamide, mescaline and 2,5-dimethoxy-4-methylamphetamine (DOM) was significantly increased by medial raphe (m-R) lesions, but dorsal raphe (d-R) lesions did not produce any changes. Hallucinogen-induced head twitch was inhibited by methysergide and tended to be increased by PCPA. These results suggest that 5-HT receptors innervated with the ascending 5-HT pathway originating in the m-R play a vital role in the manifestation of hallucinogen-induced head-twitch. That is, increase of head-twitch is ascribed to supersensitivity of 5-HT receptors. On the other hand, DOM-induced backward locomotion was inhibited by m-R or both dorsal and medial raphe lesions and methysergide, and was reversed to forward locomotion, differently from the hallucinogen-induced head-twitch. A reversion of backward locomotion was not obtained with d-R lesions or PCPA treatment.

DOM 2,5-Dimethoxy-4-Methylamphetamine↗
PubMed1992

Receptors mediating the actions of 5-hydroxytryptamine on the isolated retractor muscle of the penis preparations from Archachatina marginata (Swainson).

1. The effects of some 5-hydroxytryptamine (5-HT) receptor agonist and antagonists on the isolated retractor muscle of the penis of Archachatina marginata were investigated. 2. Both 5-hydroxytryptamine and lysergic acid diethylamide (LSD) contracted the preparations. The mean pD2 values obtained for 5-HT and LSD were 5.26 +/- 0.21 (N = 10) and 6.3 +/- 0.36 (N = 8) respectively. 3. 5-Methoxy, N,N,-dimethyltryptamine (5-MeODMT; N = 6) trifluoromethylphenylpiperazine (TFMPP; N = 6) alpha-methyl 5-hydroxytryptamine (alpha-Me-5-HT); N = 6) and both L and DL-5-hydroxytryptophan (L-5-HTP; N = 6, DL-5-HTP; N = 6) did not contract the preparations even when concentrations up to 10(-4) M were administered. 4. Ketanserin (10(-8)-10(-6) M) produced rightward shift of the concentration-response curve of 5-HT. (pA2 = 8.0 +/- 0.25, slope = 0.34 +/- 0.03; N = 6). 5. The contractions of the RMP to 5-HT were not antagonised by either LY53857 or ICS 205-930. 6. The present study does not reveal the presence of 5-HT1-like or 5HT2 receptors on the RMP. However 5-HT3 receptors do not seem to exist on this invertebrate smooth muscle.

Animals↗
PubMed1990

5-HT-induced transferrin production by choroid plexus epithelial cells in culture: role of 5-HT1c receptor.

Previous studies in our laboratory have demonstrated that serotonin (5-HT) elevates transferrin production by choroid plexus epithelial cells in primary culture in a time- and concentration-dependent fashion. The present study shows that 5-HT stimulates phosphoinositide hydrolysis in these cells and further demonstrates that the phosphoinositide hydrolysis response is mediated by the 5-HT1c receptor. To determine if the effect on transferrin is also mediated by the 5-HT1c receptor, the effects of 5-HT receptor agonists and antagonists were examined in choroid plexus epithelial cells in primary culture. The stereoisomers of lysergic acid diethylamide (LSD) and the piperazine derivative 6-chloro-2-[1-piperazinyl]-piperazine (MK-212) were evaluated as potential agonists. MK-212 and (+)LSD mimicked 5-HT, increasing transferrin levels to the same extent. The levorotary isomer, (-)LSD, had no effect. This agonist profile agrees with that previously found for 5-HT1c receptor-mediated phosphoinositide hydrolysis. Three antagonists with varying potencies to block 5-HT1c receptor-mediated phosphoinositide hydrolysis were examined: ritanserin, mianserin and spiperone. The results of these studies were less clear-cut. Neither mianserin nor ritanserin significantly reduced the effects of 5-HT on transferrin, even though they markedly reduced 5-HT-induced phosphoinositide hydrolysis. Consistent with its low potency at the 5-HT1c receptor, spiperone, a 5-HT2 and 5-HT1a antagonist, was a less effective antagonist of the phosphoinositide hydrolysis response than were ritanserin and mianserin. Spiperone also failed to block the effect of 5-HT on transferrin.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1971

Persistent increase in brain serotonin turnover after chronic administration of LSD in the rat.

Lysergic acid diethylamide at doses of 20 micrograms per kilogram per day was administered orally to rats for I month. Eighteen hours after the final dose a 25 to 30 percent increase in the synthesis and turnover of serotonin was noted, as well as a moderate but significant increase in the concentration of tryptophan (18 percent) and serotonin (13 percent) in the brain.

Administration, Oral↗
PubMed2004

Influence of menstrual cycle on platelet serotonin uptake site and serotonin2A receptor binding.

Depression and anxiety are common health problems affecting women, particularly during the reproductive years. Major depression is two to three times as common in women than in men. Neuroendocrine factors are likely to contribute to this overall increased risk for developing mood disorders in women, and the neuroendocrine influence is most obviously seen in women with premenstrual dysphoric disorder (PMDD) as these women experience depressed mood and anxiety premenstrually only during ovulatory cycles. Moreover, dysfunction of serotonergic transmission has been regarded as an important mechanism in several psychiatric disorders and ovarian steroids have been shown to profoundly influence the activity of the serotonergic system. Given these facts, the purpose of this study was to examine whether binding of [3H]paroxetine to the platelet serotonin transporter or binding of [3H]lysergic acid diethylamide ([3H]LSD) to the platelet 5-HT2A receptor are influenced by the cyclical changes in circulating estradiol and progesterone that occur during the menstrual cycle. We examined 28 healthy women, without oral contraceptives and with regular menstrual cycles. In the late follicular phase, Bmax for [3H]paroxetine binding was significantly higher than in the ovulatory (p<0.01), early luteal phase (p<0.05) and mid-luteal phase (p<0.01). Bmax for [3H]LSD binding was significantly higher in the early follicular phase and the early luteal phase compared to the mid-luteal phase (p<0.001 and p<0.05, respectively). In the early follicular phase and the ovulatory phase, significant correlations between estradiol serum concentrations and Kd for [3H]paroxetine were obtained (p<0.001, respectively). In the luteal phase, significant inverse correlations between progesterone as well as estradiol serum concentrations and Kd for [3H]LSD binding were found (p<0.05, respectively).

Adult↗
PubMed1976

Drugs and PGO waves in the lateral geniculate body of the curarized cat. II. PGO wave activity and brain 5-hydroxytryptamine.

Ponto-geniculo-occipital (PCO) waves induced either by the benzoquinolizine derivative, Ro 4-1284 (=PGO(CPA), were continuously recorded and counted in the lateral geniculate bodies of unanaesthetized immobilized cats as described in the preceding communication. The effect of various drugs interacting with central 5-hydroxytryptaminergic mechanisms on the density (number hr(-1) or number 0.5 hr(-1) of PGO waves was investigated. The density of PGO waves was dose-dependently decreased and the waves were eventually abolished by the precursors of 5-hydroxytryptamine (5-HT), L-tryptophan and 5-hydroxytryptophan. 5-HT itself, injected intracerebroventricularly, tended to diminish the density. Lysergic acid diethylamide (LSD) was an extremely potent depressor of PGO(1284) and PGO(PCPA); psilocybine was almost as potent as LSD, whereas higher doses of N,N-dimethyltryptamine, bufotenine and yohimbine were required for the reduction of PGO waves. A number of tricyclic antidepressants reduced the density of PGO waves, their order of potency corresponding to that reported for their inhibitory effect on the uptake of 5-HT; tertiary amines were more potent than secondary amines. Desipramine was more potent on PGO(PCPA) THAN ON PGO(1284). Two dibenzothiepine antipsychotics, methiothepin and octoclothepin, increased the density of PGO(1284) and PGO(PCPA) and also induced PGO waves in untreated cats; the evidence suggests that these two compounds antagonize the effect of endogenous 5-HT in the brain. These results confirm some earlier findings and augment the pharmacological pieces of evidence for the stron inhibitory influence of 5-HT neurones on the generation ofPGO waves.

Animals↗
PubMed1994

Interactions of clozapine with the stimulus effects of DOM and LSD.

Two groups of rats were trained with the 5-HT2 agonists 2,5-dimethoxy-4-methylamphetamine (DOM) or lysergic acid diethylamide (LSD) in a two-lever discrimination task. Tests of generalization and antagonism were then carried out with clozapine. DOM did not generalize to clozapine. Partial antagonism of DOM was observed with 0.3, 1, and 2 mg/kg clozapine and statistically significant full antagonism with 3 mg/kg. LSD did not fully generalize to clozapine. Partial antagonism of LSD was observed with 3 and 4 mg/kg clozapine. Because clozapine is known to block muscarinic as well as 5-HT2 receptors, atropine was studied in DOM-trained rats. DOM partially generalized to 3 mg/kg atropine. Partial attenuation of DOM stimulus effects was observed with 3 mg/kg atropine, and no attenuation with 5 mg/kg. A combination of 2 mg/kg clozapine and 3 mg/kg atropine vs. DOM produced response suppression in five of seven rats. The atropine test results do not exclude the possibility of an antimuscarinic component in the observed attenuation of DOM and LSD stimulus effects by clozapine.

DOM 2,5-Dimethoxy-4-Methylamphetamine↗
PubMedDate not supplied

LSD and creativity.

The effects of lysergic acid diethylamide (LSD) on creativity were examined in a unique experiment in the late 1950's. In this project, artists were asked to draw and paint a Kachina doll both prior to and one hour after the ingestion of LSD. Evaluations of these artistic productions were analyzed by a professor of art history in order to investigate the impact of LSD on artistic creativity. Certain representative changes were found in the artists' predominant style. The most significant change was noted in those artists whose styles were intrinsically representational or abstract to more expressionistic or nonobjective. Other changes noted included the following: relative size expansion; involution; movement; alteration of figure/ground and boundaries; greater intensity of color and light; oversimplification; symbolic and abstract depiction of objects; and fragmentation, disorganization, and distortion. Many artists judged their LSD productions to be more interesting and aesthetically superior to their usual mode of expression. The above-mentioned changes contributed to the artists' convictions that they were fashioning new meanings to an emergent world.

Art↗