Biomedical subjects

M E Meyer

Publications and source records attributed to M E Meyer.

At least 37 records · Page 2Linked to original sources

PubMed1993

Effects of intraaccumbens dopamine agonist SK&F38393 and antagonist SCH23390 on locomotor activities in rats.

The present study examined the effects of the dopamine D1 and D5 subtype receptors agonist, R(+)-1-phenyl-2,3,4,5-tetrahydro-(1H)-3-benzazepine-7,8-diol (SK&F38393), and antagonist, R(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-ben zaz epine (SCH23390), on locomotor activities after bilateral microinjection into the nucleus accumbens (Acb). SK&F38393 (0.1-10.0 micrograms) significantly potentiated and SCH23390 (0.01-1.0 microgram) significantly attenuated locomotor activity as measured by horizontal distance in cm. The data were supportive of the hypothesis that dose-related locomotor activities induced by microinjections of SK&F38393 into the Acb are independently mediated by D1 and D5 subtype receptors.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

PubMed1993

The effects of methionine-enkephalin and its related metabolites upon the duration of the dorsal immobility response in rats.

The effects of SC injections of methionine-enkephalin (Met1-5-Enk) and its N-terminal and C-terminal fragments upon the duration of the dorsal immobility response (DIR) over a 60-min time course were investigated. Experiment 1 analyzed the effects of various dosages (0.00-100.0 micrograms/kg) on DIR resulting in a potentiation of the duration in a dose-time course function. The effects of various fragments of Met1-5-Enk (10.0 micrograms/kg) from the N-terminal in Experiment 2 and from the C-terminal in Experiment 3 on the DIR resulted in the potentiation of the duration with the Met2-5-Enk and Met1-3-Enk fragments. All other fragments were not significant. The results were discussed in reference to the processing and metabolism of Met1-5-Enk.

Amino Acid Sequence↗

PubMed1993

Behavioral effects of opioid peptide agonists DAMGO, DPDPE, and DAKLI on locomotor activities.

The effects of the mu-selective agonist DAMGO (ICV doses of 0.00, 0.01, 0.1, or 1.0 micrograms), the delta-selective agonist DPDPE (ICV doses of 0.00, 0.1, 1.0, or 10.0 micrograms), and the kappa-selective agonist DAKLI (ICV doses of 0.00, 0.01, 0.1, or 1.0 micrograms) were tested in rats for 60 min in an activity monitor. The durations in seconds of linear locomotor time, rearing time, stereotypy time, and margin time (thigmotaxis) were measured during six 10-min time blocks. DAMGO (0.1 and 1.0 micrograms) resulted in biphasic effects, inhibition followed by hyperactivity for linear locomotor, rearing, and stereotypy times, and an inhibition of thigmotaxis. DPDPE (10.0 micrograms) was associated with monophasic potentiation of linear locomotor activity and mixed effects in stereotypy times. DAKLI did not effect horizontal, rearing, or margin times; only stereotypy times resulted in mixed effects of DAKLI. The differential behavioral profiles were discussed in reference to the three opioid receptor subtypes.

Amino Acid Sequence↗

PubMed1993

Intracerebral haloperidol potentiates the dorsal immobility response in the rat.

The effects of intracerebral microinjections of 4-[4-(4-chlorophenyl)-4-hydroxy-1-piperidinyl]-1-(4- fluorophenyl)-1-butanone (haloperidol) (1.0 microgram, 0.5 microliter) in five regions of the brain were tested on the duration of the dorsal immobility response (DIR) and the cling and bar catalepsy in the rat. The duration of the DIR was significantly potentiated (but not the cling and bar catalepsy) following 2-h postinjection of haloperidol in the caudate putamen, nucleus accumbens, and globus pallidus but not in the substantia nigra pars compacta or cortex. These data further expand the previous evidence of regional variations in dopamine to the effects upon inhibitory behaviors.

Animals↗

PubMed1993

Dopamine D1 receptor family agonists, SK&F38393, SK&F77434, and SK&F82958, differentially affect locomotor activities in rats.

Dopamine D1 receptor family agonists, 2,3,4,5,-tetrahydro-7,8-dihydroxy-1phenyl-1H-3-benzazepine (SK&F38393), 3-allyl-2,3,4,5-tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine (SK&F77434), and 3-allyl-6-chloro-2,3,4,5-tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazep ine (SK&F82958), were compared for their behavioral effects on horizontal movement time, rearing time, stereotypy time, and thigmotaxis time. All agonists resulted in biphasic effects with attenuation followed by potentiation (0.01-10.0 mg/kg, SC). While SK&F38393 did not potentiate horizontal movement and rearing times, and had minor effects on thigmotaxis, SK&F77434 and SK&F82958 potentiated horizontal movement and rearing behaviors and attenuated thigmotaxis. The results were discussed in terms of the binding characteristics and current receptor theory.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

PubMed1993

Behavioral effects of the mu-opioid peptide agonists DAMGO, DALDA, and PL017 on locomotor activities.

The relative role of central mu-opioid receptor agonists Tyr-D-Ala-Gly-N-Methyl-Phe-Gly-ol (DAMGO), Tyr-D-Arg-Phe-Lys (DALDA), and Tyr-Pro-MePhe-D-Pro (PL017) (0.00, 0.01, 01, or 1.0 micrograms, ICV) on behavior was investigated in rats for 60 min in activity monitors. DAMGO (0.1 and 1.0 micrograms) and PL017 (1.0 micrograms) resulted in biphasic effects, inhibition followed by hyperactivity for linear locomotor, whereas the 0.01-micrograms dosage was associated with hyperactivity. On the other hand, DALDA (0.1 and 1.0 micrograms) suppressed locomotor activity over the 60-min session.

Amino Acid Sequence↗

PubMed1993

Intrastriatal injections of dynorphin A fragments potentiate the dorsal immobility response in rats.

The effects of bilateral intrastriatal injections (2.0 micrograms/side) of Dynorphin A 1-17 (Dyn A 1-17) and Dynorphin A 1-8 (Dyn A 1-8) and their related nonopioid fragments upon the dorsal immobility response (DIR) over a 1-h time course were investigated. Dyn A 1-17 and Dyn A 2-17 potentiated the duration of the DIR 5 min postinjection, whereas Dyn A 1-8 and Dyn A 2-8 potentiated the DIR duration at each time point over the hour with their greatest effect at 15 min. An SC injection of 4 mg/kg naloxone 15 min prior to central injections blocked the potentiation of the DIR effects of Dyn A.

Amino Acid Sequence↗

PubMed1993

Effects of dopamine D1 antagonists SCH23390 and SK&F83566 on locomotor activities in rats.

The effects of the dopamine D1 antagonists R-(+)-7-chloro-8-hydroxy-3-methyl-1phenyl-2,3,4,5-tetrahydro-1-H-3 -benzazapine (SCH23390) and (+-)-7-bromo-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1- H-3-benzazapine (SK&F83566) were tested for 2 h on linear locomotor, rearing, stereotypy, and margin times in an open field. Each of the antagonists attenuated the duration of linear locomotion, rearing, and stereotypy times in a dose- and time-dependent manner. The effectiveness of the antagonists was relatively brief and SCH23390 was more effective than SK&F83566 on each behavior. The two antagonists had differential effects on margin time.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

PubMed1992

A limiting factor mediates the differential activation of promoters by the human progesterone receptor isoforms.

The two transcription activation functions (TAFs) of the human progesterone receptor (hPR) have been characterized. TAF-1, located in the N-terminal region A/B, has been narrowed down to a 91-amino acid sequence, which is sufficient for transcription activation in chimeras with the GAL4 DNA binding domain. Both hPR TAF-1 and TAF-2 activate a minimal promoter in yeast. No autonomous TAF could be found in the N-terminal 164 amino acids (designated AB3) which are responsible for the differential activation of promoters by the hPR isoforms A and B. Reduction of the target gene promoter complexity did not alter this differential activation, indicating that AB3 does not require additional promoter-bound factors to exert its effect. Instead, the cell specificity of AB3 and its ability to squelch hPR-induced transcription suggest that this differential isoform activity is due to the effect of a limiting factor which binds to region AB3.

Amino Acid Sequence↗

PubMed1992

Effects of intracerebral quinpirole on locomotion in rats.

The effects of the dopamine D2 receptor agonist quinpirole (LY 171555) on locomotor activity and margin time (thigmotaxis or wall-hugging) were measured for 2 h in rats injected either s.c. (vehicle, 0.02, 2.0 mg/kg) or directly into either the dorsal striatum or nucleus accumbens (vehicle, 0.1, 1.0, 10, 20 or 40 micrograms bilaterally in each site). In all groups, margin time decreased as drug dose increased. As in previous research, quinpirole given s.c. decreased locomotor activity at a low dose and had a biphasic effect on locomotor activity at the high dose. Both of these effects were also elicited by quinpirole injected directly into the dorsal striatum; 10 and 20 micrograms decreased locomotion immediately, while 40 micrograms led to both the immediate decrease and a later increase. In contrast, the lowest doses of quinpirole (0.1 and 1.0 microgram) injected into the nucleus accumbens led to an increase in locomotion from 20 to 60 min, while the higher doses led only to the early decrease. Thus, both the locomotor activating and inhibiting effects of quinpirole are found in both the nucleus accumbens and the dorsal striatum, but the differing dose-response relationships indicate that the mechanisms are not the same in these two brain regions.

Animals↗

PubMed1992

The effects of bilateral and unilateral vibrissotomy on behavior within aquatic and terrestrial environments.

Introducing an untreated rat to a novel environment typically results in thigmotaxis or wall-seeking behavior and the unilateral removal of the vibrissae induces an asymmetry in thigmotaxis. The present study investigated the effects of bilateral and unilateral removal of the vibrissae (vibrissotomy) upon the rat exhibiting thigmotaxis within aquatic and terrestrial environments. Unilateral vibrissotomy resulted in directional thigmotaxis asymmetry toward the intact vibrissae side within both environments. Within the aquatic environment, the unilateral vibrissotomy group swam a significantly longer distance than the other two groups. The data are discussed in terms of activation and sensory information.

Animals↗

PubMed1992

Potentiation of the dorsal immobility response following intrastriatal injections of enkephalins.

The effects of bilateral intrastriatal injections (1.0 microgram/side) of leucine5- and methionine5-enkephalins and their related nonopiate fragments upon three measures of immobility over a time course were investigated. Both leucine5-enkephalin and des-Tyr1-leucine-enkephalin potentiated the duration of the dorsal immobility response (DIR) 15 min postinjection and over a 1-h time course. On the other hand, methionine5-enkephalin and des-Tyr1-methionine-enkephalin potentiated the duration of the DIR at 5 and 15 min. These enkephalins and their fragments had no effect upon vertical cling and bar catalepsy. In a second study, an SC injection of 4 mg/kg naloxone 15 min prior to the central injections blocked the potentiation of the DIR effects of the enkephalins.

Animals↗

PubMed1992

Dopamine D1 antagonists potentiate the durations of bar and cling catalepsy and the dorsal immobility response in rats.

The effects of dopamine D1 antagonists SCH 23390 or SK&F 83566 (at SC doses of 0.00, 0.01, 0.05, and 0.1 mg/kg) were tested for 2 h on bar and cling catalepsy and the dorsal immobility response. Each of the drugs potentiated the duration of each of the three measures of immobility in a dose- and time-dependent manner. Each of the drugs had rapid but brief effects on all three response measures; the peak effect of SK&F 83566 took place at 20 min and that for SCH 23390 at 40 min for each behavior. At each effective drug dose, SCH 23390 had a greater effect than SK&F 83566 on each behavior. Dopamine D1 antagonists potentiated three different immobility responses, as do dopamine D2 antagonists.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

PubMed1992

Differential effects of dopamine D2 agonist quinpirole upon the dorsal immobility response in rats.

The effects of various dose levels of systemically injected quinpirole upon the dorsal immobility response (DIR) over a time course was investigated in male rats. A low dose of quinpirole (0.01 mg/kg) significantly attenuated the duration of the DIR following the 10-min interval, whereas the highest dose (1.0 mg/kg) had a biphasic effect so that at the 10-min interval the duration of the DIR was significantly potentiated and at the 60-min interval the duration of the DIR was significantly attenuated. The intermediate dose (0.1 mg/kg) had intermediate behavioral effects. The data support the growing evidence that quinpirole has differential effects upon behavior over time as a function of the dose levels. The present data were discussed in reference to presynaptic and postsynaptic dopamine D2 receptor theory.

Animals↗

PubMed1992

Differential effects of intrastriatal estradiol on the dorsal immobility response in male rats.

The effects of implants of 17 beta-estradiol and cholesterol in four regions of the dorsal striatum were tested on the duration of the dorsal immobility response in gonadectomized male rats. The dorsal immobility response was significantly potentiated by 4-h implants of 17 beta-estradiol in the dorsomedial and dorsolateral regions of the dorsal striatum but not in the ventromedial and ventrolateral regions. These data further support the growing evidence that estradiol acts directly but differentially on the striatum to affect behaviors in the rat.

Animals↗

PubMed1992

Mechanisms of antihormone action.

The mechanisms of action of two types of anti-hormones is discussed. Type I anti-hormones comprise the antiestrogen hydroxy-tamoxifen and the antiprogestin RU486, both of which promote DNA binding of the cognate receptors and, due to the activity of one of the two transcription activation functions of the estrogen and progesterone receptors, act as mixed agonist/antagonists. Evidence supporting that ICI 164,384 is also a member of the same group is presented. Type II antagonists impair DNA binding of the corresponding receptor in vitro and, in some cases, also in vivo. Ligand-mapping, an approach to identify the site of interaction of a steroid substitution within the hormone-binding domain of the receptor has been used to identify the 11 beta-pocket of the progesterone receptor and revealed that a single amino acid is responsible for the differential antagonistic effect of RU486 in man, chicken and hamster.

Animals↗

PubMed1991

Control of transcription of the chicken progesterone receptor gene. In vitro and in vivo studies.

To study the promoter of the chicken progesterone receptor (cPR) gene and the relevance of several progestin-responsive elements therein, chimeric genes were constructed which contained the 5'-flanking region of the cPR gene linked to promoterless globin or chloramphenicol acetyltransferase sequences. Cell-specific initiation of transcription was observed in transiently transfected chicken embryo fibroblasts when using 876 base pairs of the cPR gene upstream region. Transcription from these reporter genes could be induced by progestins in the presence of cPR form A but not of form B. In keeping with these data, three in vitro progesterone receptor (PR)-binding sites were identified in the cPR promoter region by DNase I protection assays. However, in vivo, nuclear run-on transcription demonstrated that neither primary stimulation with progestins, nor treatment of secondarily estrogen-stimulated chicks with progestins, glucocorticoids, or androgens resulted in any significant change of cPR gene transcription in the oviduct, thus suggesting a cell- and/or development-specific role for these progestin-responsive elements. Although estrogen is known to increase PR levels in the chick oviduct, this effect does not involve stimulation of PR gene transcription, as demonstrated here by nuclear run-on experiments, the analysis of DNase I hypersensitive sites, and transient cotransfection studies. Since acute withdrawal from estrogen-stimulation markedly decreased the level of cPR mRNAs in chick oviduct when analyzed by Northern blotting, we conclude that estrogen-dependent stimulation of PR levels in the oviduct is a post-transcriptional process.

Animals↗

PubMed1991

Sex differences in locomotor activity after acute and chronic cocaine administration.

Adult, intact and gonadectomized male and female Wistar rats (n = 9) were exposed to an automated open field to assess the behavioral effects of acute cocaine administration (saline, 1.0 and 10.0 mg/kg subcutaneous). The subjects were exposed to the open field for 10 min, removed to be injected and returned to the open field for another 30 min. Three saline and two drug sessions were run in counterbalanced order. Locomotor activity in intact and castrated male rats and ovariectomized female rats decreased following injection, irrespective of the dose of cocaine. The locomotor activity of intact female rats was higher than that of any other group of subjects. It decreased during the session after saline and 1.0 mg/kg cocaine, but increased towards the end of the 30 min session after 10.0 mg/kg. Rearing measures paralleled the observations on locomotor activity. To determine the effects of chronic, home-cage, cocaine administration, five of the subjects in each group were injected with 10.0 mg/kg cocaine for 9 consecutive days. The remaining four subjects received saline injections. On day 10, all subjects were re-exposed to the open-field for 10 min, removed, injected with 10.0 mg/kg cocaine and returned to the open field for another 30 min. Chronic home cage cocaine administration produced an increase in cocaine's effects on locomotor activity and rearing in intact female rats only. However, behavioral sensitization was also observed in intact female rats who had been treated with saline for 9 consecutive days, suggesting that behavioral sensitization to cocaine in intact female rats may develop very rapidly and independent of environmental context.

Animals↗