Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P80404 (GABA transaminase)
 786 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

L-Cycloserine dose-dependently inhibited the activity of gamma-aminobutyric acid (GABA)-transaminase (GABA-T) and elevated the level of GABA in whole mouse brain with a peak effect 3-4 hr after a single intraperitoneal injection. At a dose (30 mg/kg) which elevated the level of GABA almost 4-fold, L-cycloserine moderately increased the content of alanine and slightly reduced that of aspartate, glutamate and glycine in the brain. L-Cycloserine (10-30 mg/kg, p.o. or i.p.) prevented tonic seizures induced by 3-mercaptopropionic acid (3-MPA) and audiogenic seizures in DBA/2 mice, without affecting those evoked by pentylenetetrazol, bicuculline and electroshock. Similarly small doses of L-cycloserine reduced the level of cGMP in the cerebellum of rats, prevented its elevation by 3-MPA and attenuated the hypothalamically-elicited rage reaction in cats. Larger doses of L-cycloserine (greater than 30-100 mg/kg) impaired the performance of mice in the rotarod, chimney and horizontal wire tests, and reduced spontaneous locomotor activity of rats. Upon repeated administration the inhibitory effect of L-cycloserine on the activity of GABA-T and on seizures elicited by 3-MPA in mice increased. In contrast, the depressant action of L-cycloserine on motor performance and locomotion declined in subchronically-treated mice and rats. The levels of amino acids in brain after repeated administration did not differ markedly from those in acutely-treated mice. It is suggested that small doses of L-cycloserine, probably by increasing GABAergic inhibition, reduce hyperexcitability in the brain in acute- and subchronically-treated animals. Larger doses of L-cycloserine, possibly by inducing multiple neurochemical changes, evoke central depressant effects which diminish during subchronic treatment.
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PMID:L-cycloserine: behavioural and biochemical effects after single and repeated administration to mice, rats and cats. 301 1

n-di-Propylacetate (nDPA, valproate) a GABA-T inhibitor, injected IP at the dose of 300 mg/kg antagonized agonistic behavior of isolated DBA/2 mice in a time-dependent fashion in parallel to an increase of GABA levels in olfactory bulb, striatum, posterior colliculus and septum. After 75 min, aggressive responses were higher than those after 15 to 45 min and significantly lower in comparison with those of saline injected mice. After 120 min aggressive behavior was not different from that of control mice. The concentration of GABA in the striatum and olfactory bulb returned to control value 75 and 120 min after drug administration, respectively. After 120 min GABA levels in posterior colliculus and septum were lower than those after 15 to 75 min, although significantly higher in comparison with those of saline injected mice. The results are discussed in terms of the possible involvement of olfactory bulb and striatum in GABA-mediated control of isolation-induced aggressive behavior in mice.
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PMID:Effects of n-di-propylacetate on aggressive behavior and brain GABA level in isolated mice. 640 34

An inhibitor of GABA-T (sodium n-dipropylacetate), a GABA agonist (muscimol hydrobromide) and an inhibitor of GABA uptake (R,S) nipecotic acid amide were administered to DBA/2 isolated aggressive mice throughout three successive daily experimental sessions. Aggressive responses, measured by an automated device, were inhibited by the highest doses of the three drugs in each daily session. At the lowest doses, sodium, n-dipropylacetate and nipecotic acid amide failed to inhibit aggression in the first session while they were effective in the subsequent sessions. Muscimol was effective in the first session but did not differ significantly from saline in the second and third session. The highest doses of these three drugs did not affect spontaneous motor activity, indicating that the observed drug effects are rather specific.
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PMID:Effects of sodium n-dipropylacetate, muscimol hydrobromide and (R,S) nipecotic acid amide on isolation-induced aggressive behavior in mice. 677 2

The effects of drugs that antagonize or potentiate the action of brain gamma-aminobutyric acid (GABA) on shock-induced aggressive behavior in mice were investigated. In previous studies it has been shown that in C57 BL/6 strain shock-induced aggressive behavior is absent up to the 10th week of age and rises to the highest intensity after the 20th week, while at the same ages aggressive responses are lowest or absent in DBA/2 strain. GABA antagonist, picrotoxin and glutamic acid decarboxylase (GAD) inhibitor, D, L-allylglycine induced aggressive responses in non-aggressive 10 week old C57 BL/6 and 20 week old DBA/2 mice. GABA agonist muscimol hydrobromide, and GABA-T inhibitor sodium n-dipropylacetate inhibited aggressive responses in 20 week old C57 BL/6 mice. These effects were not related to changes in shock sensitivity and motor activity. The results strongly suggest that the GABAergic system is involved in the control of shock-induced aggressive behavior in mice and that this control is related to developmental and genetic factors.
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PMID:Involvement of the GABAergic system on shock-induced aggressive behavior in two strains of mice. 678 19

Previous work indicated a role for GABA and glutamate in the reinforcing effects of drugs of abuse. The present studies assessed the effects of GABAergic and glutamatergic manipulations on the reinforcing effects of nicotine as assessed by intravenous nicotine self-administration. Male Wistar rats were allowed to self-administer either of two nicotine doses under a fixed ratio or a progressive ratio schedule of reinforcement. The effects of a glutamatergic compound on nicotine self-administration in male DBA/2J mice were also explored. Finally, to assess for nonspecific effects of the drug manipulations, the effects of all test compounds on responding maintained by a food reinforcer were investigated. The pharmacological manipulations used were: gamma-vinyl-GABA (vigabatrin or GVG), an irreversible inhibitor of GABA transaminase, the GABAB receptor agonists (-)baclofen and CGP44532, and the metabotropic glutamate receptor 5 (mGluR5) antagonist MPEP. GVG, CGP44532, and (-)baclofen dose-dependently decreased nicotine self-administration on the fixed-ratio schedule, but also decreased food-maintained responding. Furthermore, CGP44532 decreased breakpoints for nicotine and food at identical doses under the progressive-ratio schedule. MPEP dose-dependently decreased nicotine self-administration with no effect on food-maintained responding in rats. MPEP also decreased nicotine self-administration in the mice. These results demonstrate that activation of GABAB receptors or blockade of mGluR5 decreased nicotine self-administration. Although there was some selectivity for the effects of the GABAergic manipulations, there was clear selectivity of the effects of MPEP on nicotine- versus food-maintained responding. Thus, compounds that increase GABAergic neurotransmission and antagonists at mGluR5 have potential as anti-smoking medications for humans.
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PMID:Role of gamma-aminobutyric acid (GABA) and metabotropic glutamate receptors in nicotine reinforcement: potential pharmacotherapies for smoking cessation. 1554 54