Hyposensitivity of dopamine "autoreceptors" induced by chronic administration of tricyclic antidepressants.
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Biomedical subjects
Publications and source records attributed to A Argiolas.
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In this preliminary report we showed that 3,4-dihydroxyphenylacetic acid (DOPAC), the major metabolite of dopamine (DA), is present in the ventral tegmental area. This finding indicates that in the ventral tegmental area, which contains the cell bodies of dopaminergic neurons of the mesocortical and mesolimbic DA systems, DA may be released by a mechanism similar to that operating in the nerve endings. However, haloperidol, which increases DOPAC levels in the substantia nigra, failed to do so in the ventral tegmental area. The results support the contention that DA neurons in the ventral tegmental area have distinctive features from nigral DA neurones.
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Electric foot-shock stress (20 min) increases DOPAC content in the frontal cortex (by about 80%) and in the nucleus accumbens (by 35%) but not in the striatum. However, foot shock stress failed to modify the kinetic properties of tyrosine hydroxylase (Vmax, Km for DMPH4 cofactor) in any of the above areas. Similar results were obtained in rats in which noradrenergic terminals in the n. accumbens and in the frontal cortex had been eliminated by injection of 6-OH-dopamine into the ascending dorsal noradrenergic bundle. The results support the hypothesis that limbic and cortical DA is involved in emotional states and indicate that DA synthesis may be regulated independently from changes in the kinetics properties of tyrosine hydroxylase.
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A radioenzymatic method for simultaneous determination of dopamine and DOPAC in small brain areas is described. By using this assay, 250 pg of dopamine and 150 pg of DOPAC can be estimated. The present method has been applied to compare the effect of different psychotropic drugs on the dopamine and DOPAC levels in the caudate nucleus, substantia nigra and medial basal hypothalamus.
Changes in brain serotonin levels are correlated with the latency of an early component of auditory evoked potentials (EAEP) in rats. In fact 5-hidroxytryptophan provokes an increase both in serotonin brain synthesis and in the latency of EAEP. On the other hand, PCPA provokes an opposite effect.
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Lithium chloride exerts two opposite effects on dopamine uptake by synaptosomes isolated from rat caudate nucleus. Added in vitro, it inhibits dopamine uptake; whereas administered chronically in vivo, it enhances dopamine uptake in vitro. Thus, in vitro, 1, 2.5, 5 and 10 meqiv.l-1 of lithium chloride decrease [3H]dopamine uptake by 13, 17, 25 and 31%, respectively. Synaptosomes isolated from rats treated with lithium chloride for 20 days, show a 23% increase in [3H]dopamine uptake with respect to synaptosomes isolated from control rats. It is suggested that chronic lithium treatment stimulates a compensatory mechanism which overcomes its direct inhibitory effect on [3H]dopamine uptake.
The intraperitoneal administration of D-amphetamine (0.2--2.5 mg/kg) decreases dihydroxyphenylacetic acid (DOPAC) content not only in the caudate nucleus but also in the substantia nigra. This effect persists both in the substantia nigra and in the caudate nucleus after loss of dopamine-sensitive adenylate cyclase and presumably of dopamine receptors, induced by intrastriatal injection of kainic acid. These results indicate that the effect of amphetamine on DOPAC levels in the nigra is not mediated through a strionigral feedback loop.
Adrenocorticotropin (ACTH)-like immunoreactivity and bioactivity were extracted from rat hypothalamus and fractionated by high pressure liquid chromatography. Analysis of the fractions either by radioimmunoassay or bioassay (corticosteroid production from rat adrenal cells) revealed several peaks of immunoreactivity and bioactivity. Only 20-25% of total ACTH-like immunoreactivity and bioactivity eluted with the same retention time as authentic ACTH 1-39. The results suggest that different forms of ACTH exist in rat hypothalamus.