Decrease In Dopaminergic Activity Research Articles

Фибрилляция предсердий и артериальная гипертензия при гипотиреоидной патологии

A special role in the formation of atrial fibrillation in patients with arterial hypertension is played by diseases of the thyroid gland. In any form of hypothyroidism, vascular tone increases, hypervolemia is formed, which leads to changes in blood pressure, myocardial dystrophy and the development of AF. The development and progression of AF affects the lack of thyroid hormones: TH suppresses aldosterone synthesis and stimulates the secretion of atrial and cerebral natriuretic peptide. Therefore, hypothyroidism develops hyperaldosteronism and decreases the content of natriuretic hormone in the blood, which leads to hypervolemia. Atrophic processes in cardiomyocytes are exacerbated by intracellular potassium deficiency, which is caused by hyper aldosteronism characteristic of all types of hypothyroidism. TG plays the role of physiological antagonists of antidiuretic hormone, and their deficiency leads to increased water reabsorption and increases the likelihood of the formation of a volume-dependent form of hypertension, the effect on the endothelium of the cell, releasing vasoactive substances and reducing the sensitivity of adrenoreceptors to the action of catecholamines. In hypothyroidism, almost all soft tissues, including the vascular wall, accumulate in an excessive amount of glycosaminoglycans, which ' ions and water, which leads to swelling of the vascular wall, reduction of nitric oxide production and narrowing of the lumen of arteries and veins. Hyperproduction of thyroliberin, which leads to a decrease in dopaminergic activity of the brain. In addition, hypothyroidism causes thickening of the basement membrane of capillaries and the diffusion of oxygen through their wall is disturbed. The effect of hypothyroidism and drugs used in its treatment on AF is ambiguous. The authors disagree about the course of AF and the frequency of relapse, the risk of complications of AF. All this indicates the need to continue research in this direction.

The dopamine D2 receptor mediates approach-avoidance tendencies in smokers.

Dopamine D2 receptors (DRD2) have been strongly implicated in reward processing of natural stimuli and drugs. Using the approach-avoidance task (AAT), we recently demonstrated that smokers show an increased approach-bias toward smoking-related cues but not toward naturally rewarding stimuli. Here, we examined the contribution of the DRD2 Taq1B polymorphism to smokers' and non-smokers' responsivity toward smoking versus naturally rewarding stimuli in the AAT. Smokers carrying the minor B1 allele of the DRD2 Taq1B polymorphism showed reduced approach behavior for food-related pictures compared to non-smokers with the same allele. In the group of smokers, a higher approach-bias toward smoking-related compared to food-related pictures was found in carriers of the B1 allele. This pattern was not evident in smokers homozygous for the B2 allele. In addition, smokers with the B1 allele reported fewer attempts to quit smoking relative to smokers homozygous for the B2 allele. This is the first study demonstrating that behavioral shifts in response to smoking relative to natural rewards in smokers are mediated by the DRD2 Taq1B polymorphism. Our results indicate a reduced natural-reward brain reactivity in smokers with a genetically determined decrease in dopaminergic activity (i.e., reduction of DRD2 availability). It remains to be determined whether this pattern might be related to a different outcome after psychological cessation interventions, i.e., AAT modification paradigms, in smokers.

Brain renin-angiotensin system and dopaminergic cell vulnerability.

Although the renin-angiotensin system (RAS) was classically considered as a circulating system that regulates blood pressure, many tissues are now known to have a local RAS. Angiotensin, via type 1 receptors, is a major activator of the NADPH-oxidase complex, which mediates several key events in oxidative stress (OS) and inflammatory processes involved in the pathogenesis of major aging-related diseases. Several studies have demonstrated the presence of RAS components in the basal ganglia, and particularly in the nigrostriatal system. In the nigrostriatal system, RAS hyperactivation, via NADPH-oxidase complex activation, exacerbates OS and the microglial inflammatory response and contributes to progression of dopaminergic degeneration, which is inhibited by angiotensin receptor blockers and angiotensin converting enzyme (ACE) inhibitors. Several factors may induce an increase in RAS activity in the dopaminergic system. A decrease in dopaminergic activity induces compensatory upregulation of local RAS function in both dopaminergic neurons and glia. In addition to its role as an essential neurotransmitter, dopamine may also modulate microglial inflammatory responses and neuronal OS via RAS. Important counterregulatory interactions between angiotensin and dopamine have also been observed in several peripheral tissues. Neurotoxins and proinflammatory factors may also act on astrocytes to induce an increase in RAS activity, either independently of or before the loss of dopamine. Consistent with a major role of RAS in dopaminergic vulnerability, increased RAS activity has been observed in the nigra of animal models of aging, menopause and chronic cerebral hypoperfusion, which also showed higher dopaminergic vulnerability. Manipulation of the brain RAS may constitute an effective neuroprotective strategy against dopaminergic vulnerability and progression of Parkinson’s disease.

Melanoma tumors alter proinflammatory cytokine production and monoamine brain function, and induce depressive-like behavior in male mice

Depression is a commonly observed disorder among cancer patients; however, the mechanisms underlying the relationship between these disorders are not well known. We used an animal model to study the effects of tumor development on depressive-like behavior manifestation, proinflammatory cytokine expression, and central monoaminergic activity. Male OF1 mice were inoculated with B16F10 melanoma tumor cells and subjected to a 21-day behavioral evaluation comprising the novel palatable food (NPF) test and tail suspension test (TST). The mRNA expression levels of proinflammatory cytokines, interleukin (IL)-1β and IL-6, and tumor necrosis factor-alpha (TNF-α), were measured in the hypothalamus and hippocampus and the levels of IL-6 and TNF-α were measured in the blood plasma. We similarly determined the monoamine turnover in various brain areas. The tumors resulted in increasing the immobility in TST and the expression level of IL-6 in the hippocampus. These increases corresponded with a decrease in dopaminergic activity in the striatum and a decrease in serotonin turnover in the prefrontal cortex. Similarly, a high level of tumor development produced increases in the brain expression levels of IL-6 and TNF-α and plasma levels of IL-6. Our findings suggest that these alterations in inflammatory cytokines and monoaminergic system function might be responsible for the manifestation of depressive-like behaviors in tumor-bearing mice.

Brain‐encysting trematodes and altered monoamine activity in naturally infected killifishFundulus parvipinnis

This paper presents novel evidence to address mechanisms by which trematode parasites effect behavioural changes in naturally infected fish hosts. California killifish Fundulus parvipinnis infected with the brain-encysting trematode Euhaplorchis californiensis display conspicuous swimming behaviours that render them 30 times more likely to be eaten by birds, the parasite's final host. Prevalence of E. californiensis reaches nearly 100% in most F. parvipinnis populations, with parasite biomass constituting almost 2% of F. parvipinnis biomass in some locations. Despite having thousands of cysts on their brains, infected fish grow and mature at rates comparable to those of uninfected populations. The lack of general pathology combined with the specificity of the altered behaviours suggests that the behavioural changes are due to parasite manipulation. The monoamine neurotransmitters serotonin and dopamine, which control locomotion and social behaviour in fishes and other vertebrates, were examined to explore the underlying mechanisms of this behaviour modification. Whereas previous studies were similarly conducted with experimentally infected fish, in this study, brain dopaminergic and serotonergic activity were analysed in naturally infected fish to assess how E. californiensis may alter F. parvipinnis monoamines in a naturally occurring system. A parasite density-associated decrease in serotonergic activity occurred in the hippocampus of naturally infected fish, as well as a decrease in dopaminergic activity in the raphe nuclei, suggesting that E. californiensis inhibits serotonin and dopamine signaling in naturally infected F. parvipinnis. The neurochemical profile of infected fish is consistent with the hypothesis that E. californiensis affects brain monoaminergic systems in order to induce impulse-driven, active, and aggressive behaviour in its hosts.

A Brief Overview of Iatrogenic Akathisia

Akathisia is a significant and serious neurological side effect of many antipsychotic and antidepressant medications. It is most often expressed as a subjective, uncomfortable, inner restlessness, which produces a constant compulsion to be in motion, although that activity is often not able to relieve the distress. Because it can be extremely upsetting to the patient, akathisia is a common cause of nonadherence to psychotropic treatment. Unfortunately, its subjective nature makes quantitative assessment difficult. Although its pathophysiology is not well-established, a decrease in dopaminergic activity appears to be an important etiological factor. In addition to reducing the dose of the offending drug, the most effective treatment of akathisia includes administration of either a beta-adrenergic antagonist or a serotonergic 5HT2 receptor antagonist. The therapeutic effect of monoaminergic antagonists is believed to result from blockade of inhibitory noradrenergic and serotonergic inputs onto dopaminergic ...

Emotion-based decision-making in healthy subjects: short-term effects of reducing dopamine levels.

Converging evidences from animal and human studies suggest that addiction is associated with dopaminergic dysfunction in brain reward circuits. So far, it is unclear what aspects of addictive behaviors are related to a dopaminergic dysfunction. We hypothesize that a decrease in dopaminergic activity impairs emotion-based decision-making. To demonstrate this hypothesis, we investigated the effects of a decrease in dopaminergic activity on the performance of an emotion-based decision-making task, the Iowa gambling task (IGT), in 11 healthy human subjects. We used a double-blind, placebo-controlled, within-subject design to examine the effect of a mixture containing the branched-chain amino acids (BCAA) valine, isoleucine and leucine on prolactin, IGT performance, perceptual competency and visual aspects of visuospatial working memory, visual attention and working memory, and verbal memory. The expectancy-valence model was used to determine the relative contributions of distinct IGT components (attention to past outcomes, relative weight of wins and losses, and choice strategies) in the decision-making process. Compared to placebo, the BCAA mixture increased prolactin levels and impaired IGT performance. BCAA administration interfered with a particular component process of decision-making related to attention to more recent events as compared to more distant events. There were no differences between placebo and BCAA conditions for other aspects of cognition. Our results suggest a direct link between a reduced dopaminergic activity and poor emotion-based decision-making characterized by shortsightedness, and thus difficulties resisting short-term reward, despite long-term negative consequences. These findings have implications for behavioral and pharmacological interventions targeting impaired emotion-based decision-making in addictive disorders.

Effect of centrally injected allopregnanolone on sexual receptivity, luteinizing hormone release, hypothalamic dopamine turnover, and release in female rats.

The effect of intracerebroventricular (icv) injection of allopregnanolone (5alpha-pregnan-3alpha-ol-20-one) on the dopaminergic and reproductive function in ovariectomized rats primed with estrogen and progesterone was investigated. Thirty minutes after icv allopregnanolone injection, the sexual receptivity, luteinizing hormone (LH) release, dopamine content, and release in the medial basal hypothalamus (MBH) and preoptic area (POA) were determined. After allopregnanolone injection, LH serum levels were reduced (p < 0.001) and lordosis behavior was inhibited (p < 0.005). Intracerebroventricular injection of bicuculline (a gamma-aminobutyric acidA [GABAA] antagonist) alone was ineffective. The injection of allopregnanolone plus bicuculline blocked the effects of allopregnanolone on sexual receptivity and on LH serum levels. At the same time, endogenous dopamine concentration in both the MBH and POA was augmented (p < 0.005 and p < 0.006, respectively) and the turnover rate decreased in both structures. Moreover, in vitro 3H-dopamine release from MBH and POA was lower in rats injected with allopregnanolone in comparison with vehicle-treated rats. These results suggest that allopregnanolone influences the dopaminergic mechanisms in female rats, which may, in turn, be responsible for the reduced reproductive activity. Allopregnanolone may exert its effects on sexual behavior through GABAA receptor modulation and a decrease in dopaminergic activity in the MBH and POA. These actions could explain the inhibition of LH release.

Biphasic effects of pu-chung-i-chi-tang on sedation and excitation.

The biphasic effects of Pu-Chung-I-Chi-Tang (PCT) on sedation and excitation in acute treatment or after one-week consecutive treatment were studied. The results indicated that PCT produces sedation in acute treatment and excitation after one-week consecutive treatment. The sedative mechanism of PCT in acute treatment might be due to an increase in serotonergic activity and a decrease in dopaminergic activity. However, the excitatory mechanism of PCT after one-week consecutive treatment might involve the increase in dopaminergic activity and the decrease in serotonergic activity.

Simultaneous measurement of biogenic amines and their metabolites in rat brain regions after acute administration of and abrupt withdrawal from butorphanol or morphine.

Changes in levels of biogenic amines and metabolites were measured using high performance liquid chromatography fitted with an electrochemical detection in various rat brain regions after acute administration of and abrupt withdrawal from continuous intracerebroventricular infusion of butorphanol (a mu/delta/kappa mixed opioid receptor agonist) or morphine (a mu-opioid receptor agonist). A single dose of butorphanol (26 nmol/5 microliters) or morphine (26 nmol/5 microliters) increased levels of 3,4-dihydroxyphenylacetic acid in the striatum and limbic region and of homovanilic acid in the cortex, striatum, and limbic region. In animals which had been infused with butorphanol (26 nmol/microliters/hr) or morphine (26 nmol/microliters/hr) for 3 days, an increase in dopamine turnover was observed. The levels of 3,4-dihydroxyphenylacetic acid was decreased and that of homovanilic acid was increased in the striatum, limbic region, and midbrain immediately after termination of opioid infusion. Both dopamine metabolites (in these areas) were decreased at 2 and 6 hr after butorphanol or morphine withdrawal. Changes in norepinephrine, serotonin, and 5-hydroxyindoleacetic acid levels in some brain regions were observed in the morphine-, but not in butorphanol-dependent rats. These data suggest that the increase and the decrease in dopaminergic activity, but not noradrenergic and serotonergic neurons, in the some brain regions are closely associated with the production of antinociception of and the expression of withdrawal syndrome from butorphanol and morphine, respectively.

Reciprocal Changes in Psychosis and Mood After Physostigmine in a Patient With Alzheimer's Disease

To the Editor.— The role of the cholinergic system in neuropsychiatric disease has been the topic of two recent articles in theArchives. 1,2 The cognitive and behavioral effects of the cholinesterase inhibitor physostigmine salicylate in patients with Alzheimer's disease has been the subject of an ongoing study. We describe the fluctuation in one patient's psychotic and depressive symptoms that were consistent with the hypotheses that associate increased muscarinic activity with depressive and negative symptoms. The patient's psychotic symptoms were alleviated, although the depressive symptoms increased with physostigmine treatment. This agent presumably increases the functional activity of acetylcholine and causes a relative decrease in dopaminergic activity (as reflected by a decrease in cerebrospinal fluid homovanillic acid). This fluctuation of symptoms and biochemical profile suggests certain parallels to patients with schizophrenia, in whom increased muscarinic activity has been associated with depressive and negative symptoms, and increased mesocorticolimbic dopaminergic activity with psychosis. 1

The elevation of immunoreactive beta-endorphin in old male rats is related to alterations in dopamine and serotonin

The concentration of immunoreactive beta-endorphin (IR-BE) in the anterior pituitary (AP) and the neurointermediate lobe of the pituitary (NIL) was elevated in old as compared to young male rats. Treatment of old male rats with the dopamine precursor, L-DOPA, did not affect the concentration of IR-BE in the AP and produced a significant reduction in the concentration of IR-BE in the NIL. By contrast, administration of the serotonergic neurotoxin, p-CPA, significantly diminished the concentration of IR-BE in the AP of old male rats, while the concentration of IR-BE in the NIL remained unchanged. Hypothalamic IR-BE was decreased in old male rats and was not influenced by administration of L-DOPA or p-CPA. Chromatographic analysis indicated that in the AP of old animals the amount of beta-endorphin relative to beta-lipotropin was increased and was diminished slightly by the treatments. Alterations in IR-BE in the NIL and hypothalamus were represented solely by beta-endorphin. These data suggest that in old male rats, a decrease in dopaminergic activity contributes to the increase in IR-BE levels in the NIL, and an increase in serotonergic function, at least in part, is responsible for the elevation in the level of IR-BE in the AP.

Opposite dopaminergic activity in lateral and median hypothalamic nuclei in relation to the feeding effect of d-Ser 2-Leu-Enk-Thr 6 (DSLET)

The Leu-enkephalin analogue d-Ser 2-Leu-Enk-Thr 6 (DSLET) had beeen shown to enhance feeding in rats, increase dopaminergic activity in the striatum like other opiate agonists, and particularly to decrease dopaminergic activity in the hypothalamus. In this study, the latter effect was found to be localized in the hypothalamic nuclei involved in the regulation of feeding such as the paraventricular (PVN), ventromedian (VMH), dorsomedian (DMH) nuclei and the lateral hypothalamus (LH). DSLET produced the same decrease in dopaminergic activity in the LH as in the whole hypothalamus. In the median nuclei (PVN and VMH and to a lesser extent in the DMH), an opposite effect was observed, resembling that in the striatum. The relevance of these opposite variations with regard to the feeding effect of DSLET is discussed. The decreased dopaminergic activity in the LH would appear to be the most specifically related to the behavioural effect given the known role of dopamine in this region. These data reconcile apparently contradictory aspects of the role of dopamine and the functional opposition between the lateral and median hypothalamus in food intake control.

Hypothermia elicited by haloperidol in rats with hypothalamic lesions

In a previous paper it was reported that haloperidol plus morphine produces a marked hypothermia, whereas each drug alone had only negligible effects on temperature. A large hypothalamic lesion produced variable hypothermia lasting several days. After the lesion, rats could be classified in two groups: A—those which had marked decreases of colonic temperature (from 3 to 7°C) and B—those which had a slight decrease (about 1°C). The administration of haloperidol, which in normal rats has no effect on temperature, elicited in hypothalamic-lesion rats, whether or not they were already hypothermic, a marked decrease in temperature lasting several hours. Rats of group B showed a faster decrease as well as a faster recovery of temperature than those of group A. It was concluded that the hypothalamic lesions produced an effect equivalent to an increase in opioid activity and/or a decrease in dopaminergic activity.

Influence of the pineal gland on pituitary function in humans

In 14 men and 14 women we examined the relationship between melatonin and the secretion of pituitary hormones. Blood pressure, and the serum concentrations of melatonin, catecholamines, prolactin, thyrotropin, growth hormone, and cortisol were determined every 3–4 hr for 24 hr. In the normal, basal (unstimulated) condition there were no significant correlations ( p > 0.05) between the systolic blood pressure and dopamine ( r = 0.09), norepinephrine ( r = 0.26), or epinephrine ( r = 0.27), nor were there significant correlations between melatonin and dopamine ( r = −0.01), norepinephrine ( r = −0.26), or growth hormone ( r = 0.17). The concentrations of melatonin correlated positively with those of prolactin ( r = 0.56, p < 0.05 for men and r = 0.58, p < 0.001 for women) and thyrotropin ( r = 0.62, p < 0.001 for all subjects), but not with those of cortisol ( r = 0.004, p > 0.05). We speculate that the increase in melatonin at night leads to a decrease in dopaminergic activity; the diminished release of dopamine may lead to a simultaneous increase in thyrotropin and prolactin.

Cerebrospinal fluid HVA, central brain atrophy, and clinical state in schizophrenia

In 16 patients with chronic schizophrenia, cerebrospinal fluid (CSF) concentrations of homovanillic acid (HVA) showed a significant negative correlation with computed tomographic measures of brain third ventricle size. Clinical state during a drug-free period was also significantly correlated with CSF HVA level, but not with third ventricle size when the effect of CSF HVA was partialed out. The authors propose that these findings may reflect an atrophic process involving structures around the third ventricle and a decrease in dopaminergic activity.

The effects of pimozide on the reinforcing efficacy of central grey stimulation in the rat.

The present report describes the effects of the neuroleptic pimozide on the reinforcing efficacy of central grey stimulation. Six adult rats were implanted with a monopolar moveable stimulating electrode in the pontine central grey. Each bar-press in an operant chamber delivered a 0.3-s train of cathodal rectangular pulses of constant duration (0.1 ms) and intensity (from 180 to 440 microA depending on the subject) and of variable frequency. The function relating the rate of bar-pressing to the logarithm of the number of pulses per train (rate-frequency function) was recorded following administration of vehicle and increasing doses of pimozide (from 0.15 to 0.5 mg/kg). Pimozide produced a dose-dependent parallel shift of the rising segment of the rate-frequency function towards higher pulse numbers in 4 subjects, indicating that the drug reduced the reinforcing efficacy of the stimulation. In two subjects, the shift was accompanied by a decrease in slope of the rising segment. Depending on the subject, the greatest shift observed varied from 0.087 to 0.489 log units. Further attempt to increase the magnitude of shift with higher doses resulted in complete abolition of self-stimulation. The fact that pimozide reduced the value of reward in an area containing only marginal amounts of dopaminergic cells adds support to the hypothesis that dopamine modulates reward indirectly. The fact that the shift could not be increased with higher doses was interpreted as an indication that dopaminergic neurons are involved in a gate-like synaptic arrangement in which a limited decrease in dopaminergic activity is sufficient to obliterate the transmission in the reward pathway or the conversion of the signal into a reinforcing effect.

Prenatal Neuroleptic Exposure Alters Postnatal Striatal Cholinergic Activity in the Rat

Previous studies in our laboratory have shown that prenatal exposure to a neuroleptic during a critical period of gestation in the rat results in a marked deficit in the number of striatal dopamine-binding sites and in a diminution of dopamine agonist-induced stereotyped behavior. In the present studies, we examined the effect of prenatal neuroleptic exposure on biochemical parameters of cholinergic activity to determine whether the balance between striatal dopaminergic and cholinergic activity might be altered. The number of muscarinic cholinergic-binding sites and the specific activity of choline acetyltransferase were found to be significantly increased by prenatal treatment with the neuroleptics haloperidol or (+)-butaclamol. From the present studies and previous observations made in our laboratory, it is concluded that the ability of a neuroleptic to affect the number of muscarinic cholinergic receptors in postnatal life may be a result of the phenotypically undifferentiated state of the developing dopamine-binding site. Our findings of increased striatal cholinergic activity accompanied by a marked decrease in dopaminergic activity may have implications for an increased vulnerability to extrapyramidal motor disturbances during postnatal development.

Increased investigative activity after presynaptic dopaminergic stimulation measured by a fixed-interval recording procedure

A fixed-interval recording procedure was used to study the effects of catecholaminergic agonists and antagonists on the exploratory behaviour pattern in male rats. One particular element of this pattern, the investigative behaviour, was found to be sensitive to drugs acting on both noradrenaline and dopamine receptors. An increase in investigate activity (IA) and a slight decrease in the other exploratory (OE) activity was caused by α-methyl-p-tyrosine. The α 2-receptor agonists clonidine and B-HT 933 decreased both the IA and the OE activity. These effects were counteracted by yohimbine. Activation of presynaptic dopamine receptors by low doses of apomorphine (⩽0.2 mg/kg) and B-HT 920 resulted in significant increase in IA and a decrease in OE activity. Higher doses of apomorphine (0.7 and 1.0 mg/kg) decreased or abolished IA but increased OE activity. We assume this effect to be due to postsynaptic receptor stimulation. Pretreatment with haloperidol counteracted the effects of apomorphine and B-HT 920. An increase in IA is probably due to a decrease in dopaminergic activity, which can be induced by presynaptic receptor activation. The decrease in IA after presynaptic noradrenergic stimulation cannot at present, however, be related to a specific influence, since the possibility of general effects on locomotion cannot be ruled out. The increase in IA observed after presynaptic dopaminergic activation and the fixed-interval recording procedure may be valuable instruments in the search for selectivily acting compounds with dopaminergic activity.

Amniotic fluid catecholamines and metabolites in intrauterine growth retardation

Simultaneous determinations of amniotic fluid levels of the catecholamines dopamine (DA), norepinephrine (NE), and epinephrine (E), and the intraneuronal metabolites of DA, 3,4-dihydroxyphenylacetic acid (DOPAC) and NE, 3,4-dihydroxyphenylglycol (DOPEG), were made, by radioenzymatic assay, in pregnancies resulting in growth-retarded (n = 14) normal (n = 63) infants. Significant elevations in the mean concentrations of (p < 0.000005), E (p > 0.0005), and DOPEG(p < 0.000001) as well as a significant decrease in the mean concentration of DOPAC (p < 0.000001) were found in pregnancies resulting in growth-retarded infants as compared to pregnancies resulting in normal infants. Amniotic fluid DOPES levels were found to be the most discriminative. As amniotic fluid catecholamines are predominantly of fetal origin, these findings suggest that an increase in adrenergic activity and a decrease in dopaminergic activity occur in intrauterine growth retardation as a response to chronic stress. (Am. J. Obstet. Gynecol. 141:608, 1981.)