Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:Q86TM3 (cage)
 29,987 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Attacks of sustained dystonia of the limbs and trunk can be initiated by handling or mild environmental stimuli (e.g. new cage) in mutant (gene symbol dtsz) Syrian golden hamsters. The severity of the dystonic syndrome in these mutant hamsters is age-dependent, with a peak at weaning (21 days of age) and a second peak at about 30-40 days of age. Spontaneous remission occurs at an age of about 70 days. The syndrome in hamsters is thus similar to transient paroxysmal dystonia in children. In the present experiments, it was examined whether dystonic hamsters exhibit age-dependent differences in susceptibility to drugs which affect GABA (gamma-aminobutyrate)ergic, glutamatergic or dopaminergic functions. After acute administration, the GABA-elevating drug aminooxyacetic acid was significantly less potent in attenuating the severity of dystonic attacks at 21 days than at 31 days of age. Similar but less marked age-dependent differences in antidystonic activity were found for phenobarbital and diazepam. In contrast to these GABAmimetic drugs, the NMDA receptor antagonist CGP 37849 (DL-[E]-2-amino-4-methyl-5-phosphono-3-pentenoic acid) or the dopamine receptor antagonist haloperidol had about the same antidystonic potency at both 21 and 31 days of age. Chronic treatment of dystonic hamsters with aminooxyacetic acid, starting at 21 days of age, did not alter the time course or the severity of dystonia.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Alterations in pharmacological sensitivity of GABAergic but not dopaminergic and glutamatergic systems during ontogenesis in dystonic mutant hamsters. 838 61

Changes in release and uptake of [3H]5-HT and [14C]GABA were compared in slices taken from the hippocampus and frontal cortex of rats, left undisturbed in their home-cages, or exposed for 5 min to the elevated plus-maze or social interaction tests of anxiety. Exposure to the plus-maze decreased cortical GABA function (shown by decreased release) and increased hippocampal 5-HT function (shown by increased K(+)-evoked release but more markedly by decreased uptake). Compared with undisturbed home cage controls, only the high light, familiar condition of the social interaction test resulted in a significant increase in K(+)-evoked release of both [3H]5-HT and [14C]GABA from the hippocampus. All four social interaction test conditions resulted in increases in cortical uptake of [3H]5-HT and all but the high light, unfamiliar condition increased cortical uptake of [14C]GABA. Analysing the two factors manipulated in the social interaction test, unfamiliarity with the test arena resulted in increased uptake of hippocampal [3H]5-HT and decreased cortical [14C]GABA, whereas an increase in the level of light decreased the cortical uptake of [14C]GABA. The results show that changes in presynaptic function occur rapidly in response to a brief exposure to animal tests of anxiety. However, only the increased hippocampal release of 5-HT is likely to be causally linked to anxiety and the results show that this cannot be the sole explanation.
 ...
PMID:Social interaction and elevated plus-maze tests: changes in release and uptake of 5-HT and GABA. 847 17

Rats were pretreated for 11 months with vehicle or with chronic haloperidol (HAL), administered either continuously (in the drinking water) or intermittently (via weekly injections). During this time the animals were habituated to an enclosed tube and periodically monitored by a computerized video device which measured their oral movements. The rats were then withdrawn from chronic HAL and bilateral cannulae were implanted in the ventrolateral striatum (VLS) and substantia nigra (SN). One week later oral movements were observed in an open cage and then measured by the computerized video device following bilateral infusions into VLS of the muscarinic agonist pilocarpine or the dopamine D1 agonist SKF38393, or following infusions of the GABA antagonist bicuculline into SN. Agonist infusions into VLS had different effects depending upon the prior regimen of chronic HAL. Infusions of pilocarpine into VLS led to an exaggeration of the distinctive oral movement form which follows continuous HAL but an attenuation of the different oral syndrome in the intermittent chronic HAL animals. Infusions of SKF38393 into VLS had similar, but considerably smaller effects. Infusions of bicuculline into SN did not induce either effect. These results indicate differences exist in either striatum or its output circuitry in the neurochemical mechanisms which mediate the different oral movement forms induced by different chronic neuroleptic regimens.
 ...
PMID:Oral movement patterns induced in rats by local infusions into striatum depend upon the regimen of prior neuroleptic exposure. 854 32

In vivo microdialysis combined with HPLC-EC analysis was used to monitor extracellular glutamate and GABA in the medial nucleus accumbens of Lister hooded rats during acquisition and expression of a conditioned emotional response. Footshock paired with tone (acquisition of conditioned emotional response) causes a significant decrease in extracellular glutamate during the period of footshock followed by a marked, but short lasting increase when the rats return to their home cage. Expression of the conditioned emotional response on exposure to the contextual cue produces no change in glutamate during exposure to the contextual cue, but a short lasting increase after. Thus, both the conditioned emotional response and footshock are associated with marked, but short lasting, increases in extracellular glutamate in the nucleus accumbens which, in both cases, occurred after the aversive stimuli, i.e., when the rats are returned to their home cage. In contrast, when control rats are exposed to the testing box without giving footshock there is an increase in extracellular glutamate during the exposure period and this is accompanied by exploratory behaviour. The conditioned emotional response (contextual cue), footshock and exposure of the control rats to the test box all resulted in increased extracellular GABA during exposure to the test situation. These results suggest that increases in extracellular glutamate in the medial nucleus accumbens caused by the conditioned emotional response or footshock are probably associated with relief from, rather than response to danger.
 ...
PMID:Extracellular glutamate in the nucleus accumbens during a conditioned emotional response in the rat. 858 69

Neural connections from the hippocampus and nucleus accumbens to the subpallidal area have been implicated by behavioral observation. The locomotor activity recorded in an automated activity cage increased substantially after the bilateral injection of carbachol, a cholinergic agonist, into the dentate gyrus of the hippocampus, and this increase of activity was reduced significantly after the injection of glutamate antagonist into the nucleus accumbens. On the other hand, this hyperactivity elicited by the injection of carbachol was also reduced by the injection of GABA into the subpallidal area. In another observation, increased locomotor activity was recorded following the injection of dopamine into the nucleus accumbens. However, the increase of locomotor activity induced by dopamine was attenuated by the injection of GABA into the subpallidal area. These observations suggest that neural connections from hippocampus and nucleus accumbens to the subpallidal region may contribute to locomotor activity.
 ...
PMID:Neural connection from hippocampus to nucleus accumbens and the subpallidal area and their contribution to locomotor activity. 869 95

In step-down test, diazepam (1 mg.kg-1 po, 1 h before training) was shown to significantly impair memory acquisition in mice. But piracetam (200 mg.kg-1 ip, 1 h before training) was found to improve the diazepam-induced impairments of learning. By photocell cage method, piracetam showed no significant inhibitory effect on the diazepam-induced spontaneous motor activity in mice. In Y-maze test, Glutamic acid (0.1 microgram, icv, 3 min before training) significantly improved learning in normal mice and the amnesic effect of GABA and diazepam were completely antagonized by Glutamic acid and piracetam (200 mg.kg-1 ip, 1 h before training). These results suggest that increasing GABA-ergic neuronal transmission is unfavorable to learning and memory, but increasing Glu-ergic transmission is contrary to the former. It seemed that the presence of Glu/GABA system in the brain could regulate learning and memory.
 ...
PMID:[Antagonism of piracetam on the amnestic effect of diazepam in mice]. 876 67

The time- and temperature-dependencies of binding are overviewed for the benzodiazepine, GABA and convulsant binding sites of the GABAA receptor-ionophore complex. Kinetic separation of the dissociation phases of a beta-carboline inverse agonist demonstrated the heterogeneity of its binding sites. The kinetics and thermodynamics of benzodiazepine binding alone do not correlate with ionophore function. The majority of the data suggest that agonist- and antagonist-preferring conformations exist for GABAA receptors. The high affinity binding of GABAA antagonists (SR 95531 and bicuculline) corresponds to the (super) low affinity binding of GABA. The correlation between the thermodynamic parameters of binding and efficacies common for GABAA and glycine receptor agonists and antagonists supports the functional similarities of these anionophore complexes. Binding kinetics of the bicyclic cage convulsants show several correlations with ionophore function because the convulsant sites are most intimately coupled to the ion channels. Kinetic interactions of the convulsant sites with the binding sites of benzodiazepines, GABA and central depressants have revealed several pharmacologically relevant allosteric GABAergic modulatory effects. Arrhenius analysis, Hammond's postulate and transition state theory were applied for the dissociation of convulsants. A kinetic model of interconvertible multiaffinity states of the convulsant sites shows correlations with the functional states of the GABAA ionophore.
 ...
PMID:From kinetics and thermodynamics of GABAA receptor binding to ionophore function. 893 44

This study examined the effect of the benzodiazepine, midazolam, on the consumption and palatability of 6% ethanol in male Wistar rats. In the first experiment, it was found that midazolam (5 mg/kg) increased home cage ethanol drinking 0-2 h after administration. Another intake experiment, in which ethanol was infused directly into the oral cavity through an indwelling catheter, also showed that midazolam (10 mg/kg) stimulated alcohol ingestion. The affective response to intraoral infusions of ethanol (1 ml during 1 min) was subsequently monitored in benzodiazepine-treated rats. Taste reactivity testing showed that midazolam (5-10 mg/kg) significantly increased the occurrence of hedonic orofacial responses and suppressed the number of passive drippings. A similar response pattern was observed following administration of diazepam (5 mg/kg) and chlordiazepoxide (10 mg/kg), but not after exposure to cis(Z)flupentixol (10 mg/kg). Midazolam also increased the incidence of hedonic responses in alcohol-naive rats with no previous access to ethanol in the home cages. Hedonic responsiveness did not appear to diminish with repeated benzodiazepine exposure: the behaviour of rats given five midazolam injections (10 mg/kg every second day) was similar to that shown by rats with no benzodiazepine pre-exposure. The increased hedonic response to ethanol induced by midazolam was blocked by pretreatment with the benzodiazepine receptor antagonist flumazenil (10 mg/kg), the latter drug exerting no effects on its own. The present results suggest that benzodiazepines, by acting on GABA(A) receptors, may facilitate ethanol intake by increasing ethanol's taste hedonic properties.
 ...
PMID:Benzodiazepines enhance the consumption and palatability of alcohol in the rat. 968 98

The interaction of several selected compounds with the binding of the cage convulsant t-[3H]butylbicycloorthobenzoate ([3H]TBOB) to membranes isolated from human embryonic kidney (HEK) 293 cells stably transfected with alpha1beta2gamma2s subtype of GABA(A) receptors was studied. Scatchard analysis of binding data revealed the existence of a single type of binding site for [3H]TBOB with a Kd of 47.06+/-4.06 nM and a Bmax value of 6.72+/-0.52 pmol/mg protein. GABA, thiopental, TBOB, picrotoxin and the neurosteroid dehydroepiandrosterone sulfate displaced concentration-dependently the binding of [3H]TBOB to this recombinant receptor. Dehydroepiandrosterone sulfate reversed the 5 microM GABA-induced inhibition of specific [3H]TBOB binding. It is concluded that membranes isolated from HEK 293 cells stably transfected with alpha1beta2gamma2s subunits exhibit specific high-affinity [3H]TBOB binding. The potency of drugs to inhibit [3H]TBOB binding mainly corresponded to that observed for the inhibition of the binding of cage convulsants to the native receptors or to transiently transfected HEK 293 cells.
 ...
PMID:[3H]t-butylbicycloorthobenzoate binding to recombinant alpha1beta2gamma2s GABA(A) receptor. 984 78

We investigated the importance of endogenous amino acids in the locus coeruleus in inescapable electric shock and conditioned fear. In naive rats and in rats exposed to noise (N), light (L) and electric shock (S) or to N + L only, the locus coeruleus was superfused with artificial cerebrospinal fluid through a push-pull cannula and the release of GABA, taurine, glutamate, aspartate, serine and glutamine was determined in the superfusate by HPLC after derivatization with o-phthaldialdehyde. Locomotor activity, arterial blood pressure and heart rate were telemetrically monitored. The placement of naive rats or conditioned rats from their home cage to a chamber provided with a grid-floor for shock virtually did not change the release rates of the amino acids in the locus coeruleus. Motility was enhanced in naive and conditioned rats to a similar extent. Blood pressure and heart rate were enhanced in conditioned rats only. Exposure to N + L + S for 5 min greatly enhanced the release rates of all determined amino acids in the locus coeruleus. In conditioned rats the increase in release of most amino acids lasted longer than in naive rats. Electric shock also enhanced motility, blood pressure and heart rate. In conditioned rats, motility and cardiovascular changes were more pronounced and/or lasted longer than in naive rats. Exposure of conditioned rats to the conditioned stimuli N + L for 5 min led to an increased release of taurine and aspartate. The enhanced release of taurine lasted 30 min. Exposure to N + L did not affect the release rates of amino acids in naive rats. N + L did not influence motility but arterial blood pressure and heart rate were elevated in conditioned rats. The findings show that inescapable electric shock enhances the release of several amino acids in the locus coeruleus, while conditioned fear selectively increases the outflow of taurine and aspartate. Moreover, conditioned fear prolongs the response of excitatory and inhibitory amino acids to electric shock. The results suggest that an excitatory amino acid (aspartate) and an inhibitory amino acid (taurine) of the locus coeruleus are implicated in conditioned fear.
 ...
PMID:Effects of inescapable shock and conditioned fear on the release of excitatory and inhibitory amino acids in the locus coeruleus. 1068 76


<< Previous 1 2 3 4 5 6 7 8 Next >>