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Biomedical subjects

J W Gibb

Publications and source records attributed to J W Gibb.

At least 127 records · Page 7Linked to original sources
PubMed1982

Altered neurochemical parameters in the brains of mice (Frings) susceptible to audiogenic seizures.

In this study, several biochemical aspects of serotonergic neurons were compared in mice susceptible to audiogenic seizures (Frings) and in mice not susceptible to audiogenic seizures (CF 1). Tryptophan hydroxylase (TPH) activity was significantly lower in brains of Frings mice compared to CF1 mice; however, brain levels of 5-HT were similar in both strains. The significantly lower TPH activity in Frings mice was due to the altered kinetic characteristics of TPH activity in this strain. TPH from Frings mice had a significantly lower apparent maximal velocity and a significantly higher affinity for the substrate, as indicated by a lower apparent Km for tryptophan. The uptake of tryptophan and accumulation of 5-HT (following pargyline) were similar in Frings and CF 1 mice. The levels of 5-HT in selected brain regions of Frings and CF 1 mice were also similar, but NE levels were higher in the cerebral cortex and DA levels were higher in the neostriatum of Frings mice. It is unclear at this point what role, if any, 5-HT plays in susceptibility to audiogenic seizures in brains of Frings mice.

Acoustic Stimulation↗
PubMed1982

Biochemical evidence for alteration of neostriatal dopaminergic function by 5,7-dihydroxytryptamine.

Unilateral injection of 5,7-dihydroxytryptamine (DHT) into the rat neostriatum markedly reduced not only striatal tryptophan hydroxylase (TPH) activity but also striatal tyrosine hydroxylase (TH) activity and dopamine (DA) concentration measured 10--15 days later. The decrease in striatal TH activity was dose related over the range of 8--32 micrograms of DHT; a dose of 16 micrograms reduced striatal TH activity to 40--50% of control, DA concentration to 38% of control, and TPH activity to 5--20% of control. Intrastriatal injection of 16 micrograms of DHT reduced TH activity in the ipsilateral substantia nigra to 51% of control. Pretreatment with amfonelic acid, a potent DA uptake inhibitor, significantly reduced the effect of DHT on striatal and nigral TH activity and striatal DA concentration without affecting the DHT-induced decrease in striatal TPH activity. Desmethylimipramine (5 and 25 mg/kg) had no effect on the DHT-induced decrease in striatal TH activity. Striatal choline acetyltransferase and glutamic acid decarboxylase activities were not decreased by 16 micrograms of DHT. The results indicate that DHT can alter dopaminergic function in the rat neostriatum through a direct effect of the drug on DA neurons.

5,7-Dihydroxytryptamine↗
PubMed1981

Methamphetamine-induced depression of tryptophan hydroxylase: recovery following acute treatment.

Acute administration of methamphetamine produced a dose-dependent depression of tryptophan hydroxylase (TPH) activity. The depression was observed in several serotonergic nerve terminal regions of the rat brain and spinal cord. Complete recovery of TPH activity following methamphetamine treatment occurred in all regions, but the time to recovery varied with the dose administered. In contrast to TPH, tyrosine hydroxylase (TH) was not affected by a single injection of methamphetamine. The data are discussed in the context of the effects of single versus repeated doses of methamphetamine on tryptophan and tyrosine hydroxylase.

Amphetamine↗
PubMed1981

Propranolol differentially blocks the methamphetamine-induced depression of tryptophan hydroxylase in various rat brain regions.

Basal tryptophan hydroxylase activity was measured in several serotonergic nerve terminal regions of the rat brain and was found to vary from one terminal region to another. Acute administration of methamphetamine produced a marked decrease in tryptophan hydroxylase activity in all serotonergic nerve terminal regions of rat brain examined. This decrease was antagonized in a regionally selective manner by propranolol. In contrast, haloperidol did not produce a similar antagonism. The results are discussed in the context of the previously reported efficacy of large doses of propranolol in some schizophrenic patients.

Animals↗
PubMed1980

Blockade of methamphetamine-induced depression of tyrosine hydroxylase by GABA transaminase inhibitors.

Tyrosine hydroxylase (TH) levels in the rat neostriatum are decreased by chronic treatment with methamphetamine. GABAergic neurons could potentially interact with the nigrostriatal dopaminergic neurons in either the neostriatum or the substantia nigra; therefore, the GABA transaminase inhibitors, amino-oxyacetic acid, gamma-acetylenic GABA and ethanolamine-O-sulfate, were evaluated for possible influences on the methamphetamine-induced decrease in TH. TH was measured by the procedure of Nagatsu et al. (1964). Methamphetamine (10 mg/kg, s.c.) was given every 6 h for 24 h. Thirty-six h after initiation of the methamphetamine treatment, neostriatal TH activity was approximately 70% of control. Concurrent administration of amino-oxyacetic acid (20 mg/kg, i.p.) or gamma-acetylenic GABA (15 mg/kg, i.p.) with methamphetamine completely blocked the TH depression. Dose-response curves were constructed for amino-oxyacetic acid and gamma-acetylenic GABA. A single intraventricular injection of ethanolamine-O-sulfate (400 micrograms/rat), 2-6 h before initiating the methamphetamine regimen, also completely blocked the TH depression. These data suggest that the striatonigral or other GABAergic systems are involved in the regulation of the functional state of the nigrostriatal dopaminergic neurons, and that enhanced GABAergic function will antagonize the effects of high doses of methamphetamine.

4-Aminobutyrate Transaminase↗
PubMed1980

Long-term effects of multiple doses of methamphetamine on tryptophan hydroxylase and tyrosine hydroxylase activity in rat brain.

Tryptophan hydroxylase (TPH) activity was measured in various rat brain regions after administering large doses of methamphetamine (METH). After four sequential doses of METH (15 mg/kg), given every 6 hr, TPH activity was decreased (to approximately 10% of control) in both the neostriatum and hippocampus. The depression of enzyme activity persisted for at least 30 days. When compared with the depression of neostriatal tyrosine hydroxylase activity, the depression of neostriatal and hippocampal TPH activity occurred sooner and was more pronounced. The depression of TPH activity was dependent on the number of doses and the amount of drug administered. Five days after one to two doses of METH, a transient recovery was observed but when four doses were given, the enzyme was depressed. No decrease in TPH activity was observed in brain areas containing serotonergic cell bodies. Agents which prevent the METH-induced decrease of neostriatal tyrosine hydroxylase activity, i.e., haloperidol, alpha-methyl-p-tyrosine and gamma-aminobutyric acid transaminase inhibitors also prevented the decrease in TPH activity caused by METH. In addition, fluoxetine, an inhibitor of 5-hydroxytryptamine re-uptake, prevented the METH-induced decrease in neostriatal and hippocampal TPH activity but did not alter the decrease in nenostriatal tyrosine hydroxylase activity.

Animals↗
PubMed1979

Influence of dopamine synthesis on methamphetamine-induced changes in striatal and adrenal tyrosine hydroxylase activity.

Methamphetamine in large doses decreases striatal tyrosine hydroxylase activity. This effect is prevented by neuroleptic agents such as chlorpromazine and haloperidol which would suggest that released dopamine may be involved in the response. To test this hypothesis, we have altered dopamine synthesis with alpha-methyl-p-tyrosine and L-Dopa and found that dopamine synthesis is necessary for the observed depression of striatal TH activity by methamphetamine. In the adrenal gland, however, the increase in TH activity by methamphetamine is not prevented by inhibition of catecholamine synthesis. It is possible that released dopamine may be inhibiting TH activity by activation of pre- or postsynaptic dopamine receptors in the neostriatum resulting in activation of the neuronal feedback pathway or released dopamine may act on dendrodendritic autoreceptors in the substantia nigra.

Adrenal Glands↗
PubMed1976

Influence of methamphetamine on nigral and striatal tyrosine hydroxylase activity and on striatal dopamine levels.

In previous reports, methamphetamine was shown to depress tyrosine hydroxylase (TH) activity in the rat corpus striatum. To evaluate further the mechanism of this decrease in TH activity, enzyme activity was measured in the rat corpus striatum and substantia nigra after repetitive and single-dose methamphetamine administration. Following repeated doses of methamphetamine, nigral TH activity decreased and reached 45% of controls at 12 hr and returned to normal at 60 hr. Striatal TH activity decreased to 40% of control at 36 hr and returned toward normal at 60 hr. When methamphetamine was administered every 6 hr for 30 hr and then discontinued, nigral TH activity returned toward control levels 4 days prior to recovery of striatal TH activity. Methamphetamine initially increased striatal dopamine levels at 6 hr (170% of control). Dopamine levels then decreased in parallel with striatal TH activity but failed to increase as the enzyme recovered. Concurrent administration of chlorpromazine with methamphetamine prevented the methamphetamine-induced decrease in nigral and striatal TH activity and striatal dopamine levels. The results indicate that the methamphetamine-induced depression of striatal and nigral TH activity may be related to increased stimulation of dopamine receptors in the striatum.

Animals↗