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Biomedical subjects

K Gale

Publications and source records attributed to K Gale.

At least 109 records · Page 6Linked to original sources
PubMed1981

beta-Phenylethylamine reversal of chlorpromazine-induced activation of striatal tyrosine hydroxylase and catalepsy.

The ability of beta-phenylethylamine (PEA) to reverse (1) chlorpromazine-induced activation of striatal tyrosine hydroxylase, and (2) catalepsy produced by chlorpromazine, was examined. PEA, in a dose of 75 mg/kg, caused approximately 50% reduction in the degree of tyrosine hydroxylase stimulation produced by 20 mg/kg chlorpromazine. After 150 mg/kg PEA, complete reversal of tyrosine hydroxylase activation and partial reversal of catalepsy was observed. In these experiments, PEA was found to be about 10 times less potent than amphetamine and 25 times less potent than apomorphine. Thus, the ability of PEA to reverse the neurochemical and behavioral effects of striatal dopamine blockade is similar to known dopamine agonists.

Animals↗
PubMed1981

Relationship between the presence of dopaminergic neurons and GABA receptors in substantia nigra: effects of lesions.

Submaximal destruction of nigrostriatal dopaminergic projections resulted in a significant (25%) decrease in specific GABA binding in substantia nigra; under these conditions, striatal tyrosine hydroxylase activity was 15-44% of control. In rats with lesions which caused maximal destruction of nigrostriatal dopamine neurons (striatal tyrosine hydroxylase was less than 15% of control), specific GABA binding in substantia nigra was apparently not different from that obtained in intact controls. Two distinct processes may be occurring in response to the destruction of dopamine neurons: (1) the loss of GABA binding sites physically associated with nigral dopamine neurons; and (2) an increase in nigral GABA receptors associated with non-dopaminergic neurons. The latter process may result from a decrease in nigral GABA transmission secondary to the complete loss of dopaminergic synaptic activity in striatum.

Animals↗
PubMed1981

Differential effects of gamma-aminobutyric acid (GABA)-elevating agents on the neuroleptic-induced activation of striatal tyrosine-hydroxylase: evidence that di-n-propylacetate augments GABAergic neurotransmission.

Di-n-propylacetate (DPA), in contrast to many other agents which elevate brain gamma-aminobutyric acid (GABA) content, appears to increase GABA selectively in a compartment that is associated with nerve terminals. In order to determine whether the DPA-induced increase in nerve-terminal GABA could augment GABAergic transmission in substantia nigra, we examined the ability of DPA to influence nigrostriatal dopamine function. For this purpose, the neuroleptic-induced activation of striatal tyrosine hydroxylase (TH) was selected as a model system. Neuroleptic drugs, such as haloperidol, cause an allosteric activation of striatal TH which can be measured in vitro as a decrease in the Km of TH for cofactor (2-amino-4-hydroxy-6,7-dimethyl-5,6,7,8-tetrahydropterine). This effect can be reversed by treatment with GABA-receptor agonists. We therefore examined the ability of DPA to reverse the activation of striatal TH induced by haloperidol. DPA was able to reverse the haloperidol-induced activation of striatal TH in doses which caused a 30 to 50% increase in GABA in substantia nigra. The action of DPA was completely antagonized by treatment with bicuculline, a GABA-receptor antagonist, indicating that the effect of DPA is mediated via GABA receptors. The effect of amino-oxyacetic acid was also examined, since our previous evidence suggested that the GABA increase after this agent was largely associated with compartments of GABA other than nerve terminals. Amino-oxyacetic acid was less effective than DPA in preventing the haloperidol-induced activation of TH, despite the fact that nigral GABA was increased by 30 to 100%.

Aminooxyacetic Acid↗
PubMed1980

Benzodiazepine receptors: the effect of GABA on their characteristics in human brain and their alteration in Huntington's disease.

The characteristics of bezodiazepine (BDZ) receptors were studied in the putamen and substantia nigra (SN) of control and Huntington's disease (HD) human brains. In the putamen, there was a significant decrease in density BDZ receptors in the HD tissue. In addition the application of GABA significantly potentiated DBZ receptor binding in both the HD and control putamen. In the SN, an increase in BDZ receptor density was detected in the HD tissue. GABA enhanced [3H]flunitrazepam binding in both the HD and control SN by increasing the affinity of BDZ receptors for [3H]flunitrazepam. The results suggest that there are alterations in BDZ receptors in HD human brain and that these alterations may be related to the neuronal pathology of this disease. This study also provides evidence for a coupling of GABA receptors to BDZ receptors in human brain.

Aged↗
PubMed1980

Seizure protection and increased nerve-terminal GABA: delayed effects of GABA transaminase inhibition.

Changes in gamma-aminobutyric acid (GABA) occurring in the presence and in the absence of GABA-containing nerve terminals were estimated in rats in which the dense GABA projection to the substantia nigra was surgically destroyed on one side of the brain. The net increase in GABA of the denervated nigra was compared with that of the intact nigra at various times after a single injection of gama-vinyl-GABA, which irreversibly inhibits GABA transaminase. Total GABA reached a maximum within 12 hours, but the GABA pool associated with nerve terminals did not increase until 36 hours and peaked at 60 hours. The onset and peak of anticonvulsant activity against maximal electroshock seizures directly paralleled the time course for the increase in GABA in nerve terminals, but was not positively correlated with that independent of the terminals. This result supports the concept that elevating GABA in nerve terminals facilitates GABA-mediated synaptic transmission and predicts anticonvulsant activity.

4-Aminobutyrate Transaminase↗
PubMed1979

Autoradiographic localization of neuroleptic and dopamine receptors in the caudate-putamen and substantia nigra: effects of lesions.

The localization of neuroleptic receptors was studied in the caudate-putamen (CP) and the zona compacta of the substantia nigra using light microscopic autoradiography of 3H-spiperone binding sites. Lesion of the dopaminergic input to the caudate-putamen produced an increase in receptors in the CP, possibly reflecting denervation supersensitivity. Kainic acid lesions and decortication produced significant decreases of 61% and 18% in striatal receptors. This suggests that in the caudate-putamen most of the dopamine receptors are on intrastriatal neurons, but some are also localized to the afferents from the cortex. Lesion of the nigro-striatal dopaminergic pathway produced a large (48%) decrease in receptor sites in the substantia nigra zona compacta while kainic acid intrastrially and striato-nigral pathway lesions had no significant effect. These results suggest that the majority of dopamine receptors in the zona compacta which bind neuroleptics are located on cell bodies and processes of dopaminergic neurons and are anatomically distinct from dopamine-stimulated adenylate cyclase sites.

Animals↗
PubMed1979

Dissociation between drug-induced increases in nerve terminal and non-nerve terminal pools of GABA in vivo.

To examine whether increased GABA levels produced by n-dipropylacetate (DPA) and amino-oxyacetic acid (AOAA) are associated with nerve terminals, we compared the effect of these drugs on the GABA content of substantia nigra (SN) in rats in which the GABAergic afferent projections to SN had been unilaterally destroyed. In the SN largely devoid of GABAergic nerve terminals, AOAA (30 mg/kg) produced a 2-fold increase in GABA, whereas DPA (300 mg/kg) was without effect. Since DPA and AOAA both increased GABA to a similar extent in the intact SN, it appears that the GABA increase produced by DPA is associated with GABAergic nerve terminals, while AOAA primarily elevates GABA in non-nerve terminal components (neural perikarya and glial cells) which are not destroyed by our lesions.

Aminooxyacetic Acid↗
PubMed1979

GABA receptor control of parasympathetic outflow to heart: characterization and brainstem localization.

Blockade of gamma-aminobutyric acid (GABA) receptor function by direct microinjection of the GABA receptor antagonist bicuculline into the nucleus ambiguus of the brainstem produced a marked, dose-related depression of heart rate and blood pressure which was mediated by the vagus nerve. This effect was not obtained in other regions of the brainstem and was reversed by the GABA receptor agonist muscimol. These data indicate that the nucleus ambiguus may be the site of a GABA receptor-mediated inhibition of vagal outflow.

Animals↗