The effect of repeated administration of antidepressant drugs on the thyrotropin-releasing hormone (TRH) content of rat brain structures.

The present study investigated the effect of repeated treatment with the antidepressant drugs imipramine, amitryptyline, citalopram and mianserin (10 mg/kg PO, twice daily for 14 days) on levels of thyrotropin-releasing hormone (TRH) in several brain structures (cerebral cortex, amygdala + pyriform cortex, hippocampus, nucleus accumbens, striatum and hypothalamus) of the rat. Amitriptyline caused a marked increase in the TRH content in the striatum and nucleus accumbens. Citalopram and mianserin produced a smaller but significant increase in the TRH content in the striatum only, while imipramine did not significantly affect the TRH concentrations in any of the brain structures. None of the antidepressant drugs administered acutely significantly affected the TRH concentrations in the nucleus accumbens or the striatum. These results indicate that changes in brain TRH induced by antidepressant drugs are not related to their therapeutic activity.

[Prolactin-secreting neurons in the dorsolateral hypothalamus in Sprague-Dawley rats]. / Neurones à prolactine dans l'hypothalamus dorso-latéral du rat Sprague-Dawley.

By means of immunocytochemical techniques ovine prolactin like immunoreactivity (oPRL-LIR) has been demonstrated in the perikarya located around fornix in the dorso-lateral part of the rat hypothalamus. No PRL-LIR was observed in the arcuate n. perikarya. Immunoreactive fibers were present in the hypothalamus, medial thalamus, accumbens and amygdaloid nuclei.

Aspartame and the rat brain monoaminergic system.

A high dose of aspartame (APM) was administered to rats to study possible effects on brain monoaminergic systems. APM and its metabolite phenylalanine (Phe) were given orally at doses of 1000 and 500 mg/kg, respectively. Significant increases were seen in brain Phe and tyrosine (Tyr) levels. Two different approaches were used to study monoaminergic systems: whole tissue measurements by HPLC-ED and in vivo voltammetry in freely moving rats. Dopamine, serotonin and their metabolites were taken as indexes of neuronal activity. In spite of the high dose used, no modification was found in monoamines or their metabolites in striatum, hippocampus and nucleus accumbens.

Central catecholamines, cognitive impairment, and affective state in elderly schizophrenics and controls.

Central catecholamine concentrations were determined in autopsy samples from older schizophrenic and control subjects for both the hypothalamus and the nucleus accumbens. The results of these analyses and demographic variables were regressed on antemortem measures of cognitive function and mood state. In the hypothalamus, there are significant direct relationships of homovanillic acid (HVA) and 3-methoxy-4-hydroxyphenylglycol (MHPG) with depressed mood, as measured by an adaptation of the Hamilton Rating Scale for depression. In the nucleus accumbens, dopamine (DA) and MHPG had significant inverse relationships with antemortem cognitive function, as measured by an adaptation of the Mini Mental State Exam. Results in this sample indicate that after controlling for age, the catecholamine concentrations accounted for approximately 50% of the variance in the antemortem measures of mood or cognition, depending on the loci measured.

Acute and repeated administration of sulpiride alters Met-and Leu-enkephalin content of rat brain.

Following acute administration of sulpiride (100 mg/kg, i.p.), Met-enkephalin levels were increased in striatum but decreased in substantia nigra and nucleus accumbens. No effect was observed in hypothalamus or frontal cortex. In contrast, Leu-enkephalin content was decreased in the nucleus accumbens but not elsewhere. Administration of sulpiride (10 or 100 mg/kg, i.p.) for 21 days, followed by 2 days drug withdrawal, caused a dose-dependent increase in Met-enkephalin in nucleus accumbens but decreases in hypothalamus and frontal cortex. No change was observed in the striatum or substantia nigra. Repeated sulpiride administration caused a decrease in Leu-enkephalin content of the hypothalamus and cortex but not elsewhere.

Effects of neurotensin on regional concentrations of norepinephrine in rat brain.

The effects of intraventricular administration of either 7.5 or 30 micrograms neurotensin on norepinephrine concentrations were examined in several brain regions at 5 or 30 min post-injection. Significant elevations in the level of this amine were found in the hypothalamus, nucleus accumbens and amygdala. Levels in striatum, ventral tegmentum, septum, frontal cortex and substantia nigra were not affected. The effects were most prominent 5 min after injection. Results are discussed in terms of behavioral changes induced by these doses of neurotensin.

Age-related changes in neurotensin content and receptors in various rat brain areas.

Neurotensin immunoreactivity (NT-IR) is significantly reduced in striatum, nucleus accumbens and hippocampus but not in frontal cortex, hypothalamus and septum of 24-month-old male Sprague Dawley rats. Neurotensin binding in cortex, striatum, hypothalamus and hippocampus shows a rather uniform decline with age. The changes in NT-IR content in striatum and nucleus accumbens are of particular interest in view of the existence of a functional relationship between dopamine and neurotensin.

Circadian changes in extracellular ascorbate in rat cortex, accumbens, striatum and hippocampus: correlations with motor activity.

We have used linear sweep voltammetry with carbon-paste electrodes to monitor changes in the ascorbate signal simultaneously in rat frontal cortex, nucleus accumbens, striatum and hippocampus together with motor activity. The relative amplitude of the ascorbate signal recorded in the four regions corresponded to the relative density of excitatory amino acid (EAA) transmission determined by other methods; this result provides further evidence that the ascorbate signal may be used as an index of EAA release. Changes in motor activity were associated with changes in the ascorbate signal; linear regression analysis for motor activity versus the ascorbate signal revealed differences between the release of ascorbate in the four brain regions.

An excitant amino acid projection from the medial prefrontal cortex to the anterior part of nucleus accumbens in the rat.

High-affinity uptake of neurotransmitter substrates in synaptosome-containing homogenates and tissue concentrations of amino acids were examined in subcortical areas 5-6 days after bilateral N-methyl-D-aspartate lesions confined to rat medial prefrontal cortex. D-[3H]Aspartate (32% of control) and [3H] gamma-aminobutyric acid ( [3H]GABA) (60% of control) uptakes were significantly reduced in medial prefrontal cortex, whereas [3H]choline (110% of control) uptake was unchanged, suggesting the production of axon-sparing lesions. The uptake of D-[3H]aspartate (76% of control), but not of [3H]GABA or [3H]choline, was significantly reduced in nucleus accumbens, with no concomitant reduction in amino acid concentrations. When examined in serial coronal sections, reduced D-[3H]aspartate uptake was confined to the most anterior 500 micron of nucleus accumbens (67% of contralateral sample). No significant reductions of uptake or amino acid concentrations were observed in caudate putamen or ventral tegmental area. These results suggest a role for glutamate or aspartate as neurotransmitters in projections from medial prefrontal cortex to anterior nucleus accumbens. Medial prefrontal cortex may represent the major excitatory cortical input to the nucleus accumbens.

The effects of a single acute dose of dexamethasone on monoamine and metabolite levels in rat brain.

Twenty male Sprague-Dawley rats were injected intraperitoneally with either 20 micrograms of dexamethasone or an equivalent volume of saline. The rats were then sacrificed at either one or four hours after the injections and their brains analyzed for monoamine and metabolite content using High Performance Liquid Chromatography with Electrochemical Detection. Significant effects were seen in dopaminergic and serotonergic systems, but these effects varied depending on the area of rat brain studied. Significant increases in dopamine (DA) levels were seen in the hypothalamus and nucleus accumbens of the dexamethasone treated rats when compared with saline treated rats. There was no significant effect of dexamethasone on DA levels in frontal or striatal brain areas. In the dexamethasone treated rats a significant increase in serotonin (5-HT) was observed in the hypothalamus; a significant decrease in 5-HT was observed in the frontal cortex. Biological and clinical implications of these findings are discussed.

[A TRH analog (DN-1417). Effects on the levels of monoamines and the metabolites in the various brain regions in rats].

The effects of a TRH (thyrotropin-releasing hormone) analog, DN-1417 (gamma-butyrolactone-gamma-carbonyl-L-histidyl-L-prolinamide citrate), on the levels of norepinephrine (NE), dopamine (DA), serotonin (5-HT) and the metabolites in the various brain regions of rats were determined by means of high performance liquid chromatography with electrochemical detection. DN-1417 (20 mg/kg, i.p.) produced marked decreases in the levels of NE, DA and 5-HT, especially in the nucleus accumbens, striatum and hypothalamus. The maximum effect was observed at 15 min after the administration. DA metabolites, 3,4-dihydroxyphenylacetic acid and homovanillic acid, increased significantly in the nucleus accumbens, striatum and hypothalamus, whereas 3-methoxy-4-hydroxyphenylglycol and 5-hydroxyindoleacetic acid remained unchanged. 3-Methoxytyramine increased significantly in the nucleus accumbens and striatum. Two week chronic administration of DN-1417 (20 mg/kg, i.p.) increased the levels of DA and NE in the nucleus accumbens and DA in the striatum. These results suggest that DN-1417 stimulates the turnover of the cerebral monoamines, especially the release of DA from the nucleus accumbens and striatum in the mesolimbic and nigro-striatal DAergic systems.

Postmortem central catecholamines and antemortem cognitive impairment in elderly schizophrenics and controls.

Central catecholamine concentrations were determined in autopsy brain samples from 19 elderly schizophrenic patients and controls. Data from the hypothalamus and nucleus accumbens demonstrate altered catecholamine metabolism associated with cognitive impairment in these subjects. Both loci show decrements of norepinephrine concentrations, while the nucleus accumbens samples also show increased dopamine, dihydroxyphenylacetic acid, and 3-methoxy-4-hydroxyphenylglycol concentrations associated with dementia in these subjects. The data argue for examination of catecholamine metabolism with respect to dementia in a broad range of elderly subjects.

Seasonal variation in human central dopamine activity.

This report focuses on two studies of seasonal variation of central dopamine activity in patients with schizophrenia and normal controls. In the two investigations, data were grouped and analyzed by season (i.e., spring-summer vs. fall-winter). The first study concerned blink rate, a putative measure of central dopamine activity; the blink rate for patients with schizophrenia was significantly increased during the spring-summer period. In the second study concentrations of catecholamines and their metabolites were measured in the hypothalamus and nucleus accumbens of normal and schizophrenic subjects. Findings include a reduced concentration of hypothalamus dopamine in normal controls and a reduced concentration of homovanillic acid in the nucleus accumbens of patients with schizophrenia, both during the spring-summer period.

The schizophrenia syndrome. Examples of biological tools for subclassification.

Six biological variables-platelet monoamine oxidase activity, urine phenylethylamine concentration, brain norepinephrine concentration, abnormalities on computerized tomography, lateralization asymmetries, and the presence or absence of tardive dyskinesia-are used to discriminate possible biological groups of schizophrenic patients. All variables successfully subclassify patients, some into divisions consistent with phenomological, psychosocial, or biochemical descriptions or hypotheses of schizophrenia. None of the measures, however, has sufficiently stood the test of time to be of clinical utility.

Gamma-aminobutyric-acid deficiency in brain of schizophrenic patients.

Gamma-aminobutyric acid (G.A.B.A.) was measured in the nucleus accumbens and thalamus of brains from patients who had died with schizophrenia or Huntington's chorea (H.C.) and from control subjects. Mean G.A.B.A. content was significantly reduced in both brain areas in schizophrenia and in H.C. Extraneous factors, such as age, interval from death to necropsy, cause of death, and drug use, did not readily explain the observed reduction in brain G.A.B.A. G.A.B.A. deficiency may be a biochemical characteristic of some forms of schizophrenia.

Brain-noradrenaline and 3-methoxy-4-hydroxyphenylglycol in Parkinson's syndrome.

1. Significantly reduced values of noradrenaline in Parkinson's disease were observable in all brain areas which were studied. 2. A topographic distribution of free 3-methoxy-4-hydroxyphenylglycol (MHPG) can be demonstrated in the human brain. As MHPG in the various brain areas shows a different pattern of concentration it seems that this metabolite of noradrenaline is of physiological significance and is able to reflect noradrenaline turnover. The highest values of free MHPG were found in the hypothalamus, n. accumbens, thalamus and n. ruber. 3. In a limited series of patients with Parkinson's disease post mortem analysis indicated lower values of MHPG in caudate n., putamen, s. nigra, red nucleus and n. accumbens. All other brain areas did not show significant alterations. 4. Parkinsonian patients who died during Madopar therapy demonstrated a significant increase of MHPG in caudate n., putamen, s. nigra, n. ruber, n. amygdalae and n. accumbens when compared to the untreated group, indicating an enhanced turnover of noradrenaline in these areas. 5. Bound MHPG has been estimated in various brain areas as to be in the range of 13--38 percent of free MHPG.