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L C Murrin

Publications and source records attributed to L C Murrin.

69 records · Page 4Linked to original sources
PubMed1979

Dompamine receptors in the rat frontal cortex: an autoradiographic study.

Literature findings indicated that injection of low doses of [3H]spiperone results in a labelling of dopamine receptors in rat brain, but also in a labelling of serotonin receptors. Administration of pipamperone, a drug with serotonergic properties, to animals treated with [3H]spiperone reduced the serotonergic component of the binding and permitted an easier identification of dopamine receptor binding. At the level of Forceps Minor, there were elevated levels of receptors in the deeper layers of the cingulate cortex, in the region above the rhinal sulcus and in an area dorsal to the accumbens. This distribution is in agreement with the results of other biochemical, histochemical and electrophysiological studies.

Animals↗
PubMed1979

Neuroleptic and dopamine receptors: autoradiographic localization of [3H]spiperone in rat brain.

Rats were administered [3H]spiperone (SP: spiroperidol) by tail vein injection and 2 h later the brain was processed for light microscopic autoradiography. High densities of autoradiographic grains were found in all areas known to have a dopaminergic innervation, including the olfactory tubercles, nucleus accumbens, nucleus caudate-putamen, lateral septum, zona incerta, nucleus subthalamicus, arcuate nucleus, nucleus of the central amygdala, areas in the ventral tegmentum and the claustrum. There were also increased autoradiographic grain densities in other areas such as the midbrain and the frontal cortex indicating that binding occurred to other neurotransmitter receptors besides dopamine receptors. These studies delineate with a high resolution at an anatomical level the major binding sites for neuroleptic drugs in the forebrain. They suggest which areas of the brain are the most involved in neuroleptic drug action and they add further evidence that important regions are those receiving a dense dopaminergic innervation.

Animals↗
PubMed1977

Autoradiographic localization of [3H]reserpine binding sites in rat brain.

[3H]Reserpine was administered (i.v.) to rats and they were killed 7 days later. At this time, the regional localization of radioactivity paralleled the distribution of specific binding sites observed in other laboratories. Autoradiographic studies of certain areas displayed a striking localization of radioactivity. There was a marked association of autoradiographic grains with areas containing catecholamine systems. In particular, the locus ceruleus, the caudate-putamen, the nucleus accumbens, the dorsolateral septum and the infundibulum had high grain densities. In the caudateputamen, there was a clear localization of grains to the neuropil. There was also a striking association of autoradiographic grains with certain hypothalamic nuclear, i.e., the dorsal premammillary nucleus, the prelateral mammillary nucleus and the lateral mammillary nucleus. In these areas, the grains were clearly localized in the cytoplasm of the cell bodies. All of the above localizations of autoradiographic grains were blocked by administration of unlabeled reserpine before injection of [3H]reserpine. The significance of these findings and their relationship to the clinical actions of reserpine are discussed.

Animals↗
PubMed1976

Dopaminergic neurons: reversal of effects elicited by gamma-butyrolactone by stimulation of the nigro-neostriatal pathway.

In vivo studies demonstrate that administration of gamma-butyrolactone, a precursor of gamma-hydroxybutyric acid causes a rapid increase in endogenous levels of striatal dopamine and an increase in tyrosine hydroxylase activity measured by following the short term accumulation of dihydroxyphenylalanine. The increase in dopamine produced by GBL is blocked by stimulation of the nigro-neostriatal pathway. If dopamine is allowed to accumulate for 30 min following administration of GBL this increased dopamine can be released by stimulation of the nigro-neostriatal pathway. Maintenance of neuronal activity in the nigro-neostriatal pathway by continuous stimulation at a physiological frequency of 3/s effectively blocks the ability of GBL to cause an increase in tyrosine hydroxylase activity in the striatum on the stimulated side. Tyrosine hydroxylase activity in the non-stimulated contralateral striatum is increased over 100% by administration of GBL. Stimulation of the nigro-neostriatal pathway 30 min after GBL administration causes about a 500% increase in the accumulation of dihydroxyphenylacetic acid in the striatum on the stimulated side. These results suggest that the increased dopamine is present in a pool which is releasable by neuronal stimulation and is subsequently exposed to MAO. These results are also consistent with the hypothesis that GBL activates tyrosine hydroxylase and increases endogenous dopamine levels primarily by blocking impulse flow in central dopaminergic neurons.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1976

Central dopaminergic neurons: effects of alterations in impulse flow on the accumulation of dihydroxyphenylacetic acid.

Stimulation of the nigro-neostriatal or mesolimbic dopamine pathway results in a stimulus dependent increase in the accumulation of dihydroxyphenylacetic acid (DOPAC) in the neostriatum and olfactory tubercles, respectively. A block of impulse flow induced pharamacologically by administration of gamma-butyrolactone or by placement of a lesion in the dopamine pathway results in a decrease in the steady state levels of DOPAC. Drugs which have previously been shown to alter impulse flow in central dopaminergic neurons also produce a predictable change in the brain levels of DOPAC. Drugs which increase impulse flow in nigro-neostriatal or mesolimbic dopamine neurons increase DOPAC levels in the striatum and olfactory tubercles and drugs which reduce impulse flow cause a reduction in DOPAC. Pargyline, a monoamine oxidase inhibitor, causes a rapid depletion of striatal DOPAC suggesting that this metabolite is rapidly cleared from the brain. Administration of benztropine, a potent inhibitor of dopamine reuptake, causes a significant decrease in striatal DOPAC and partially prevents the stimulus-induced increase in the accumulation of DOPAC. These observations together with the finding that about 85% of the DOPAC in the striatum disappears when the dopamine neurons in the nigro-neostriatal pathway are destroyed suggests that the majority of striatal DOPAC is formed within the dopaminergic neurons and may reflect the metabolism of dopamine which has been released and recaptured. We conclude that short-term changes in brain levels of DOPAC appear to provide a useful index of alterations in the functional activity of central dopaminergic neurons.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1976

Free and conjugated dihydroxyphenylacetic acid: effect of alterations in impulse flow in rat neostriatum and frontal cortex.

Stimulation of the nigro-neostriatal dopamine pathway results in an accumulation of both free and conjugated dihydroxy-phenylacetic acid (DOPAC) in the rat neostriatum. Drugs which have previously been shown to alter impulse flow in central dopaminergic neurons also produce predictable changes in the levels of both free and conjugated DOPAC in both the neostriatum and, in most cases, in the frontal cortex. Drugs such as the antipsychotics which increase impulse flow in the nigro-neostriatal dopamine neurons increase both free and conjugated DOPAC levels in both the neostriatum and frontal cortex. Drugs which reduce impulse flow, such as d-amphetamine and apomorphine, cause a reduction in free DOPAC in both the neostriatum and frontal cortex but reduce DOPAC conjugate only in the neostriatum. Pargyline, a monoamine oxidase inhibitor, causes an extensive depletion of free and conjugated DOPAC in both the striatum and frontal cortex, indicating that these metabolites are rapidly cleared from both of these brain areas.

3,4-Dihydroxyphenylacetic Acid↗