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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

Hypothalamic site of action for N-methyl-D-aspartate (NMDA) on LH secretion.

Excitatory amino acids have been shown to increase luteinizing hormone (LH) secretion following ventricular or systemic administration. In the present study we attempted to determine possible hypothalamic sites of action for the potent excitatory amino acid agonist, N-methyl-D-aspartate (NMDA). The ability of NMDA to enhance LH release was tested in male rats following infusion into the medial preoptic nucleus (MPO), anterior hypothalamic nucleus (AHY), ventromedial hypothalamic nucleus (VMH), and arcuate nucleus (ARC). In the MPO, infusion of 50 or 500 pmole NMDA increased pituitary LH secretion, resulting in a 2-7 fold increase in plasma LH. The 50 pmole dose was selected to test more caudal hypothalamic sites. Plasma LH levels were not affected following microinfusion of NMDA (50 pmole) into the AHY, VMH, and ARC. The present results indicate a regional specificity for NMDA in the enhancement of LH secretion. This regional specificity may reflect either a greater density of LHRH perikarya in the MPO or the presence of specific amino acid receptors on neuronal elements in the MPO, but not on neuronal elements in the other areas tested.

Animals↗
PubMed1989

Serotonin-antagonist effects of 1-(1-naphthyl)piperazine on operant behavior of squirrel monkeys.

1-(1-Naphthyl)piperazine (1-NP) has been reported to have serotonin antagonist properties at the 5-HT2 subtype of receptor, and it has been suggested that it may have agonist actions at the 5-HT1 site. In the present experiments, the effects of 1-NP alone and in combination with a variety of 5-HT agonists, were studied in squirrel monkeys performing under a number of reinforcement schedules. The phenalkylamine hallucinogen 4-bromo-2,5-dimethoxyamphetamine (DOB, 0.01-0.3 mg/kg), which is thought to have predominant actions at 5-HT2 sites, reduced responding under fixed-interval (FI) schedules of presentation of food, and these decreases were blocked by 1-NP (0.3-1.0 mg/kg) or by the selective 5-HT2 antagonist, ketanserin (0.3 mg/kg). 1-(1-Naphthyl)piperazine also antagonized the decreases in responding produced by quipazine (0.1-5.6 mg/kg), another agonist with predominant 5-HT2 actions. 1-(m-Chlorophenyl)piperazine (mCPP, 0.1-3.0 mg/kg) and 1-(m-trifluoromethylphenyl)piperazine (TFMPP, 0.1-3.0 mg/kg), both thought to act primarily at 5-HT1 sites, also decreased responding and this effect was blocked by methysergide and by 1-NP, but not by ketanserin. The effects of 1-NP (0.3-5.6 mg/kg) given alone were not like those of mCPP or TFMPP. 1-(1-Naphthyl)piperazine produced moderate increases in responding under shock-avoidance schedules, whereas only decreases in responding were seen after mCPP and TFMPP.(ABSTRACT TRUNCATED AT 250 WORDS)

DOM 2,5-Dimethoxy-4-Methylamphetamine↗
PubMed1990

Growth properties and in vitro life span of Alzheimer disease and Down syndrome fibroblasts. A blind study.

A blind study was set up to examine the in vitro growth characteristics of skin fibroblasts from 2 individuals with and 9 at risk for familial Alzheimer disease, 4 individuals with sporadic Alzheimer disease, 18 with Down syndrome as well as 5 younger and 6 older controls. Several variables (biopsy size, number of explants, medium, passage procedure) were standardized. Two growth characteristics were examined quantitatively: (i) the actual in vitro replicating life span was determined by counting the number of cells plated the previous week at 500,000 cells/flask (cumulative population doublings); and (ii) the growth potential was examined by a colony size distribution assay. A difference from the age-matched controls in the growth characteristics of skin fibroblasts was only observed for two patients with and one older individual at risk for familial Alzheimer disease. The growth properties of skin fibroblast cultures from patients with sporadic Alzheimer disease or Down syndrome were not at variance with their age-matched controls. The decrease in the growth potential observed in the familial Alzheimer disease fibroblasts is however modest and needs confirmation. It is clear that the growth properties of skin fibroblasts, as examined in this study, do not provide a good marker for any form of Alzheimer disease, nor do they provide an appropriate in vitro system to study factors which may contribute to the etiopathogenesis of Alzheimer disease or Down syndrome.

Adult↗
PubMed1990

Hemangioblastoma of the lateral ventricle.

A case of hemangioblastoma of the right lateral ventricle is presented. Only five other cases of intraventricular hemangioblastoma have been reported. The literature on supratentorial intraventricular hemangioblastoma is reviewed.

Adult↗
PubMed1996

Lymphocytic infundibulohypophysitis presenting in the postpartum period: case report.

BACKGROUND: Lymphocytic adenohypophysitis is a well-known autoimmune disorder affecting the anterior pituitary gland. Posterior pituitary gland function can be impaired by a similar autoimmune disorder called lymphocytic infundibulohypophysitis. Only very few cases have been reported. CLINICAL PRESENTATION: We present a patient with central diabetes insipidus in the postpartum period. On radiologic and endocrine evidence lymphocytic involvement of the pituitary stalk and infundibulum was suspected. INTERVENTION: A diagnostic pterional craniotomy was performed. The diagnosis of lymphocytic infundibulohypophysitis was confirmed by biopsy. CONCLUSION: We present a case of lymphocytic infundibulohypophysitis. In view of its autoimmune pathophysiology the occurrence of this disorder in the postpartum period is not surprising, even though it has not been reported before. This rare disorder should be distinguished from the more common lymphocytic adenohypophysitis.

Adult↗
PubMed1977

Further studies on BL-3912A: effects on avoidance behavior of rats with low baselines and on reaction thresholds to electric footshock.

Rats selected for their low performance baselines in an active avoidance shuttle box task were given various doses of R-(-)-2-amino-1-(2,5-dimethoxy-4-methylphenyl) butane (BL-3912A), S-amphetamine or piracetam. BL-3912A at 1 mg/kg IP had no significant behavioral effects, while 5 and 10 mg/kg significantly increased the number of avoidance responses without affecting responses during the intertrial interval (ITI). Statistically reliable effects on behavior were not observed following 20 mg/kg of BL-3912A. S-Amphetamine at 0.5 and 1 mg/kg IP also facilitated avoidance responding, but could be differentiated from BL-3912A in that the S-amphetamine significantly increased shuttles during the ITI. S-Amphetamine at 0.1 mg/kg was not effective, while 2 mg/kg increased ITI activity. Piracetam (50 or 200 mg/kg) had no significant effects on avoidance or shuttles during ITI. Using an electric shock titration procedure, BL-3912A at 10 and 20 mg/kg IP had no significant effect on reaction thresholds. Animals receiving 100 mg/kg of p-chlorophenylalanine po for 3 days and tested 2 days later showed hyperalgesia to the electric shock. In summary, BL-3912A facilitated shuttle box avoidance responding of rats with low performance baselines. Behavioral facilitation occurred without concomitant increases in noncontingent activity or apparent changes in reactivity to electric footshock.

DOM 2,5-Dimethoxy-4-Methylamphetamine↗
PubMed1981

Effects of a new type of 5-HT receptor agonist on male rat sexual behavior.

8-Methoxy-2-(di-n-propylamino) tetralin (8-OMe-DPAT) and 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) are two new drugs exerting selective actions on brain 5-HT neurotransmission. In the present experiments we have investigated the effects of these two drugs on male rat sexual behavior. It was found that both drugs reduce the number of intromissions preceding ejaculation and shorten the ejaculation latency. These effects are extremely pronounced and several animals ejaculate at the first intromission. In addition 8-OH-DPAT produced a slight reduction of the post-ejaculatory interval. There were no significant effects on latency to initiate copulation or in the number of mounts preceding ejaculation. Finally, sexual behavior was partly or completely restored in castrated male rats after injection with 8-OMe-DPAT or 8-OH-DPAT.

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

A behavioral comparison of Nexus, cathinone, BDB, and MDA.

The effects of 4-bromo-2,5-dimethoxyphenethylamine (Nexus), 3,4-methylenedioxyamphetamine (MDA), 3,4-methylenedioxyphenyl-2-butanamine (BDB), and cathinone were studied in the newly hatched chicken and compared to the effects of d-amphetamine and three hallucinogens in the same species. Cathinone, a psychomotor stimulant in man (6), produced effects that were qualitatively similar to effects seen after administration of d-amphetamine (i.e., distress vocalization, wing extension, inability to stand, and loss of righting reflex). BDB, a compound with unknown activity in man, and two known hallucinogens, Nexus (5) and MDA (1), produced effects in the chicken that are common to both stimulants and hallucinogens in this species. For example, both MDA and BDB produced abnormal body posture that was identical to that reported after administration of hallucinogens such as lysergic acid diethylamide (LSD) and harmine (11). Nexus, on the other hand, produced rigid penguin-like posture, an effect seen in the chicken after administration of another hallucinogen, mescaline (12). BDB also produced bursting forward movements, an effect commonly observed after LSD and harmine. Our findings suggest that the young chicken can be used as an alternative, nonmammalian, model for predicting classification of new compounds.

DOM 2,5-Dimethoxy-4-Methylamphetamine↗
PubMed1996

Behavioral effects of the putative anxiolytic (+/-)-1-(2,5-dimethoxy-4-ethylthiophenyl)-2-aminopropane (ALEPH-2) in rats and mice.

Behavioral effects of the phenethylamine derivative (+/-)-1-(2,5-dimethoxy-4-ethylthiophenyl)-2-aminopropane (ALEPH-2) were studied in mice and rats. Murine locomotor activity, measured with a photocell actometer, was markedly depressed following IP injection of 2 and 6 mg/kg of the drug. The same doses of the drug also decreased frequency and duration of head dipping and the number of rearings in the hole board apparatus. In the murine elevated plus maze 2 and 6 mg/kg of ALEPH-2 increased the percentage of both open arm entries and time. The total number of entries into the enclosed arms was not significantly affected by the drug. In the rat, 2-12 mg/kg ALEPH-2, IP, decreased photobeam counts in the actometer in a dose-dependent fashion. Both 2 and 4 mg/kg of the drug increased the percentage of open arm entries, but only the highest dose significantly increased the percentage of time spent on the open arms. The dose of 4 mg/kg ALEPH-2 also significantly decreased the total number of enclosed arm entries. Finally, in a recently developed model of anxiety and memory, the elevated T-maze, the doses of 2 and 4 mg/kg ALEPH-2 did not change inhibitory avoidance of the open arms. Nevertheless, the highest dose had an amnestic effect on this task, repeated 72 h later in the absence of drug. In addition, this dose significantly increased the latency to escape from the open arms and had an amnestic effect measured 72 h later. Overall, these results indicate that ALEPH-2 possesses anxiolytic, amnestic as well as sedative and/or motor depressant actions.

DOM 2,5-Dimethoxy-4-Methylamphetamine↗
PubMed1987

Tectal transplants into the occipital cortex of the newborn rat.

Embryonic day 15 rostral tectum (presumptive superior colliculus) was transplanted into the occipital cortex of newborn rats. One to two months later, the transplants were visualized and injected with either horseradish peroxidase (HRP) or wheat germ agglutinin conjugated with HRP (WGA/HRP). After the appropriate survival time and processing with either diaminobenzidine (DAB) or tetramethylbenzidine tetrahydrochloride (TMB), HRP-labelled pyramidal cells were found in layer V of the host ipsilateral occipital cortex. Thus, the occipitotectal connections are formed between host and graft despite the fact that the fibers must grow in a direction opposite to their normal course to reach the aberrantly positioned tectal graft.

Animals↗
PubMed1996

Production of tumor necrosis factor in spinal cord following traumatic injury in rats.

Production of tumor necrosis factor (TNF) in the spinal cord following traumatic injury has been studied. In these experiments, the level of TNF was examined in the homogenate of the spinal cord, cerebrospinal fluid (CSF) and serum (n = 56). TNF could be detected in the injured spinal cord but not in the normal spinal cord. The TNF level increased in the spinal cord after the injury. At the lesion site, a maximal TNF concentration was observed 1 h after the injury, and the TNF concentration remained at this level until 8 h after the injury. Thereafter, it decreased gradually. However, TNF still could be detected 72 h after the injury. No TNF could be detected in the CSF and serum, collected from rats both with and without spinal cord injury (SCI). This study thus suggests that TNF is produced locally in the spinal cord following traumatic injury, and this TNF production is caused by the injury. The present results also demonstrate that TNF production is an acute and rapid reaction in the spinal cord following traumatic injury.

Animals↗