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D X Freedman

Publications and source records attributed to D X Freedman.

At least 37 records · Page 2Linked to original sources
PubMed1988

Serotonin2 agonist administration down-regulates rat brain serotonin2 receptors.

Daily administration of D-lysergic acid diethylamide (LSD) was previously shown to decrease serotonin2 (5-HT2) receptor binding in rat brain. Recently, 4-substituted derivatives of 1-(2,5-dimethoxyphenyl)-2-aminopropane, the substitution being with either iodine (DOI) or bromine (DOB), have been suggested to be relatively selective 5-HT2 agonists. These compounds share common behavioral and neurophysiological effects with LSD, suggested to be 5-HT2 receptor mediated, and the purpose of the present study was to determine whether they also affect 5-HT2 receptor binding after systemic administration in a similar way to LSD. Administration of DOI (1.0 mg/kg) or DOB (0.5 mg/kg) for 7 days resulted in a decrease in 5-HT2 binding, as evaluated with [3H]ketanserin, similar to the decrease after LSD. In a further evaluation of the parallelism of LSD and 5-HT2 agonists, it was found that 24 hr after one administration of a low dose of LSD (130 ug/kg) or DOI (1.0 mg/kg), there was no change in binding, but there was a decrease 24 hr after a high dose (LSD, 650 micrograms/kg; DOI, 7.0 mg/kg). Four hours after the high dose of LSD or DOI there was also a decrease in 5-HT2 binding. Thus, results have shown that 5-HT2 agonists are capable of down-regulating 5-HT2 receptors and that LSD acts in a parallel fashion. This study has also demonstrated that 5-HT2 receptors can be modified within hours after drug administration.

DOM 2,5-Dimethoxy-4-Methylamphetamine↗
PubMed1988

Effects of LSD-25 on classical trace conditioning.

This study examined the effects of LSD-25 on the excitatory properties of auditory conditioned stimuli as a function of the interstimulus interval. The rabbit's eyeblink response was conditioned using a discriminative trace procedure by the pairing of a 500-msec auditory conditioned stimulus with a 100-msec shock unconditioned stimulus at intervals of 1000, 2000, 4000 and 8000 msec. Animals were able to acquire conditioned responses across all intervals. They then received doses of 35 or 85 micrograms/kg of LSD-25 prior to additional conditioning sessions. LSD-25 produced an increase in the magnitude of conditioned responses to both the positive and negative conditioned stimuli at all interstimulus intervals. It was concluded that LSD did not alter discriminative conditioning but rather enhanced the excitatory properties of both positive and negative conditioned stimuli.

Animals↗
PubMed1987

Whole blood serotonin in autistic and normal subjects.

Whole blood serotonin and tryptophan were measured in 87 normal subjects and in 40 autistic subjects. Whole blood serotonin concentrations (mean +/- SE) were significantly higher in drug-free (N = 21) autistics (205 +/- 16 ng/ml) than in normals (136 +/- 5.4 ng/ml). The Gaussian distribution of serotonin levels in the unmedicated autistic group suggests the elevation was not due to a subgroup of autistic subjects. Autistics medicated with anticonvulsants or neuroleptics had significantly lower serotonin levels than did drug-free autistic subjects. Whole blood tryptophan levels and platelet counts were similar in the autistic and normal groups. The possible causes of the hyperserotonemia of autism are discussed.

Adolescent↗
PubMed1986

Hallucinogenic drug research--if so, so what? Symposium summary and commentary.

The conference brought a critical focus both on older findings and new strategies in hallucinogenic drug research as well as on behavioral and electrophysiologic tools that correlate with neurobehavioral and neurochemical events. A number of unsolved problems to be investigated were noted. The sensitizing effects of both mescaline and LSD on other inputs at motor nuclei or at limbic sites, and effects on afferent processes were examples of important new directions as were drug discrimination tests that can determine the relative roles of aminergic systems in drug effect. Fixed ratio operant schedules can differentiate serotonin blocking agents, detect active indole psychotomimetics and demonstrate temporal and tolerance parameters relevant to drug induced neurochemical changes. Data and critique as well as pharmacokinetics no longer support the presynaptic-disinhibition model of LSD effects, nor is LSD induced "slowed turnover" of serotonin seen as an accurate description of neurochemical changes. The distinct nerve ending biochemical changes after LSD are reviewed. Subcellular compartmental analyses require a radical revision of the picture of the ratio in the nerve ending of cytoplasmic and vesicular amine as well as factors normally regulating accessibility of amine to intraneuronal MAO.

Animals↗
PubMed1985

Daily LSD administration selectively decreases serotonin2 receptor binding in rat brain.

The effect of ten daily injections of saline or d-lysergic acid diethylamide (LSD) (260 micrograms/kg i.p.) on serotonin1 (5-hydroxytryptamine1, 5-HT1) and 5-HT2 receptor binding was determined in brain membranes from rats killed 24 h after the last injection. [3H]LSD (3.0 nM) was used with either 30.0 nM 5-HT or 70.0 nM cinanserin to estimate 5-HT1 and 5-HT2 receptors, respectively. LSD administration decreased 5-HT2 binding in cortex, striatum, hippocampus, and diencephalon/midbrain without altering 5-HT1 or total specific binding.

Animals↗
PubMed1982

Rat brain aryl acylamidase: further characterization of multiple forms.

1. Two fractions of aryl acylamidase (EC 3.5.1.13) were further separated from rat brain extracts at pH 7.5 by ammonium sulfate precipitation and Bio-Gel chromatography. 2. 1,2,3,4-Tetrahydro-beta-carboline competitively inhibited (67%) fraction-1 but slightly inhibited (13%) fraction-2. Tetrahydroharman, 6-hydroxy-tetrahydroharman and harminic acid slightly inhibited both fractions. Harmalol inhibited fraction-1 but enhanced fraction-2. 6-Methoxy-harman, 6-methoxy-harmalan and harmaline enhanced both fractions. 3. Pargyline did not affect either fraction. Methiothepin, cyproheptadine and chlorimipramine inhibited fraction-1 but stimulated fraction-2. 4. Neostigmine moderately (30%) inhibited AAA-2 but did not have any significant effect on AAA-1. 5. These results indicate that the beta-carboline compounds might play a role in regulating activity of AAA-1 and 2 in brain. 6. Both fractions might be related to serotonergic neurons but only AAA-2 might be associated with acetylcholinesterase.

Amidohydrolases↗
PubMed1982

The raphe neuronal system and serotonergic effects of LSD.

Earlier work from this laboratory had shown that LSD caused significant increases in rat brain serotonin (5-HT). The increase was later localized to a subsynaptosomal fraction consisting largely of synaptic vesicles. However, the source of the increase and the mechanism by which LSD caused the enhanced 5-HT binding or retention had not been elucidated. The present study was undertaken to evaluate the serotonergic effects of LSD following destruction of raphe nuclei with radiofrequency lesions. When LSD was given to animals with large midbrain raphe lesions, it caused significant increases in forebrain of cortical 5-HT up to 48 hr, or 7 days post-lesion, respectively. It was concluded that an intact cell body is not necessary for the expression of the LSD-mediated increases in 5-HT occurring in the nerve-ending. The possible mechanisms by which LSD could act directly at the nerve-ending are discussed.

Animals↗