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Journal Article 2014; 35(5): 385-392 PubMed PMID: 25275260 Citation  Keywords:  Animals, Basolateral Nuclear Complex:cytology, Dopamine:metabolism, Dopamine Agents:metabolism, Dopamine Antagonists:pharmacology, Dopaminergic Neurons:physiology, Excitatory Postsynaptic Potentials:drug effects, Male, Organ Culture Techniques, Presynapti.   

OBJECTIVES: Dopaminergic signaling in the basolateral amygdala (BLA) is important for emotion-related activity. However, little is known about the influence of dopamine (DA) on excitatory synaptic transmission of pyramidal neurons in BLA at early developmental stage. Here in this study, we observed the effect of DA on excitatory neurotransmission in the pyramidal cells of BLA in acute slices.

METHODS: Acute slices from amygdala of rats at the age of 14-16 days were prepared and maintained in vitro using standard method. Whole-cell patch clamp recordings were performed to examine the evoked excitatory postsynaptic current (eEPSC), spontaneous excitatory postsynaptic current (sEPSC) and miniature excitatory postsynaptic current (mEPSC). Drugs including DA and synaptic blockers were added in recording solution due to different experimental designs.

RESULTS: We found that bath application of DA at a concentration of 100 μM significantly inhibited the amplitude of evoked EPSC. However, the amplitude and frequency of mEPSC were not affected. We also found increased pair pulse facilitation after DA application, indicating DA inhibited excitatory neurotransmission through suppression of release probability at the pre-synaptic terminals. Importantly, DA was also effective in decreasing activity induced upregulation in sEPSCs. Moreover, the DA effects were not affected by either antagonist of dopamine 1 or dopamine 2-like receptors.

CONCLUSION: We studied the effects of DA on excitatory neurotransmission and found that DA inhibited glutamatergic synaptic transmission via modulation of pre-synaptic release probability....

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Journal Article 2011; 32(2): 170-175 PubMed PMID: 21552201 Citation  Keywords:  Animals, Cell Proliferation:drug effects, Dopamine:metabolism, Dose-Response Relationship, Drug, Ethanol:pharmacology, Female, Glutamic Acid:metabolism, Hypothalamus:drug effects, Models, Animal, Neurotransmitter Agents:metabolism, Norepinephrine:metaboli.   

OBJECTIVES: Alcohol induces hyperprolactinemia in both alcoholic men and women, but the mechanism is not fully established. The aim is to investigate the mechanism involved in elevation of serum prolactin level after chronic alcohol administration.

METHODS: In this study, healthy female SD rats were given alcohol for 8 weeks and checked for serum prolactin level by radioimmunoassay. Interior pituitary cell proliferation was determined by immunohistochemistry score of Ki-67, and hypothalamic neurotransmitters were detected by Coulomb HPLC electrochemical array.

RESULTS: We demonstrated that serum prolactin level and wet pituitary weight of alcohol-fed rats were significantly increased. Interior pituitary cell proliferation was significantly enhanced; hypothalamic dopamine, 5-HT and GABA levels were reduced while glutamate level was increased by chronic alcohol administration; hypothalamic noradrenalin level remained unchanged.

CONCLUSION: Our study suggested that chronic alcohol administration resulted in elevated serum prolactin level in normal SD rats probably through enhancing pituitary gland cell proliferation combined with altered hypothalamic neurotransmitters that regulate prolactin level....

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Journal Article 2007; 28(5): 535-540 PubMed PMID: 17984933 Citation  Keywords:  Antiparasitic Agents:pharmacology, Antipsychotic Agents:pharmacology, Delusions:complications, Dopamine:metabolism, Dopamine Agents:pharmacology, Energy Metabolism, Humans, Insulin Resistance, Parasitic Diseases:complications, Psychological Theory, Schizo.   

: Recent meta-analyses have provided a comprehensive overview of studies investigating Toxoplasma gondii antibodies in schizophrenic patients, thus attempting to clarify the potential role these infections might play in causing schizophrenia. Issues for further research have been suggested. Associations and theories that may enrich the current level of knowledge with regard to this significant subject deserve attention. Anti-parasitic agents as well as antipsychotics are effective in treating parasitosis. Both classes of drugs have been shown to exert dopaminergic activity. Parasites and human organisms have a long history of mutual contact. The effect of parasitosis on the host and the host's response to infection are undoubtedly the product of a long evolutionary process. The neurochemical background of delusions of parasitosis is potentially similar to ancient evolutionary traces of altered neurotransmission and neuropeptide gene expression caused by parasites; these include fungal and viral infections. This is very unique in medicine if a class of drugs is effective in the treatment of an illness but also cures the delusion of the same disorder as well. Furthermore, metabolic disturbances such as hyperglycemia and insulin resistance were reported several decades before the antipsychotic era. Toxoplasmosis may also be linked to insulin resistance. Schizophrenia research can benefit from understanding this evolutionary link. New chemical entities that are liable to alter neurochemical changes related to the brain's perception of the risk of predation secondary to parasites may result in new approaches for the treatment of psychosis. These findings suggest that further research is needed to clarify this evolutionary link between parasite infection and delusions of parasitosis. We believe this model may well open up new avenues of research in the discovery of drugs to counteract schizophrenia....

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Journal Article 2006; 27(6): 799-802 PubMed PMID: 17187009 Citation  Keywords:  Adult, Catechol O-Methyltransferase:genetics, Czechoslovakia, Dopamine:metabolism, Exploratory Behavior:physiology, Female, Humans, Male, Methamphetamine, Polymorphism, Single Nucleotide, Substance-Related Disorders:enzymology,.   

OBJECTIVES: Measurable traits of human personality may mark the predisposition to psychopathology. Increased novelty seeking plays an important role in the pathogenesis of substance abuse. Novelty seeking, one of the fundamental traits of the human temperament, is related to dopamine. Catechol-O-methyltransferase (COMT) is essential for dopamine inactivation. The aim of our study was to assess whether the COMT gene Val158Met functional polymorphism in patients dependent on methamphetamine is related to their novelty seeking score.

METHODS: Patients dependent on methamphetamine who had been treated at the Addiction Treatment Unit in Nechanice in 2004 and 2005 agreed to participate in the investigation. We administered the Temperament and Character Inventory (TCI) questionnaire, assessed their novelty seeking score and analysed their DNA samples for COMT Val158Met genotype.

RESULTS: The subjects were thirty-seven Czech Caucasians (women N=10) dependent on methamphetamine with an average age of 23.6+/-3.8 years. We found a significantly higher mean novelty seeking score among the patients with the Met allele (Met/Met homozygotes+Val/Met heterozygotes; N=28) than in nine Val/Val homozygotes (27.4 vs 24.1; p=0.042, Two-Sample T-Test).

CONCLUSION: The Met allele of the COMT gene Val158Met polymorphism is associated with low COMT enzyme activity and high endogenous dopamine synaptic levels in the prefrontal cortex. This leads to a decrease in dopaminergic neurotransmission in nucleus accumbens and a need for an increased activity to stimulate it. Novelty seeking behavior corresponds with this need....

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Clinical Trial 2006; 27(3): 355-358 PubMed PMID: 16816832 Citation  Keywords:  Aged, Amyotrophic Lateral Sclerosis:drug therapy, Analysis of Variance, Dopamine:metabolism, Erythropoietin:metabolism, Female, Humans, Hypothalamo-Hypophyseal System:drug effects, Injections, Intravenous, Male, Middle Aged, Neuroprotective Agents:metabol.   

OBJECTIVES: The presence of erythropoietin (EPO) and its receptors in several central nervous system regions indicates additional functions beside its hematopoietic role. Preclinical data suggest that it may slow down the process of neuronal loss, and that EPO may cause dopamine release, and thus influence hormone release, especially prolactin. This possibility has not yet been studied in humans.

METHODS: During a clinical trial on possible protective effects in patients with amyotrophic lateral sclerosis (ALS), we studied the acute effects of EPO administration on prolactin, the release of which is under tonic inhibition of hypothalamic-pituitary dopaminergic activity. Prolactin as well as EPO levels were estimated in blood samples taken every 30 min over 2 hours after administration of 3000 IU EPO i.v. in seven male and four female patients with ALS.

RESULTS: The baseline PRL levels of the 11 patients were all within normal range (4.5-10.5 ng/ml). EPO administration caused a significant reduction in prolactin levels, maximal at 60 min after administration. Reductions in PRL were not related to EPO dose (IU per kg body weight), or to duration of illness.

CONCLUSIONS: The findings indicate that EPO promotes dopamine release in humans, and is consistent with preclinical data showing that EPO releases dopamine from rat striatal slices. Previous reports showed that dopaminergic neurons express EPO receptors, which exert a facilitating action on dopamine release, and the present data indicate that this may hold true in humans....

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Journal Article 2005; 26(1): 35-38 PubMed PMID: 15726017 Citation  Keywords:  3-Oxo-5-alpha-Steroid 4-Dehydrogenase:metabolism, Animals, Aromatase:metabolism, Brain Chemistry:physiology, Catecholamines:metabolism, Chromatography, Thin Layer, Dopamine:metabolism, Female, Feminization:physiopathology, Hypothalamus:metabolism, Male, N.   

OBJECTIVES: To study the role of opioids in early postnatal changes of the hypothalamic testosterone metabolism and catecholamine content underlying feminizing effect of prenatal stress on male sexual behavior in rats.

MATERIAL AND METHODS: 10 day-old male and female offspring from mothers given naltrexone prior to daily 1-hour restraint during the last gestational week were used in the study. Aromatase and 5 alpha-reductase activities, noradrenaline and dopamine contents in the brain preoptic area and medial basal hypothalamus were studied by thin layer chromatography, radiometric and spectrofluorimetric techniques.

RESULTS: Sexual dimorphism of testosterone metabolism enzymes activity and catecholamine content in discrete brain regions of 10 day-old rat pups was found. Prenatal stress attenuated these gender-related differences. Naltrexone pre-treatment of stressed dams prevented modifying effect of prenatal stress on aromatase activity and noradrenaline content in the male preoptic area.

CONCLUSIONS: The results of the study demonstrate preventive effect of naltrexone on stress-induced alterations of testosterone aromatization and noradrenaline concentration in the developing brain preoptic area associated with neuroendocrine control of the male sexual behavior in adult rats. These findings indicate that endogenic opioids mediate detrimental effect of prenatal stress on neurochemical determinants of the brain sexual differentiation that may underlie feminization of the male sexual behavior....

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Journal Article 2004; 25(6): 435-437 PubMed PMID: 15665806 Citation  Keywords:  Aged, Alzheimer Disease:cerebrospinal fluid, Cognition Disorders:cerebrospinal fluid, Depression:cerebrospinal fluid, Dopamine:metabolism, Female, Homovanillic Acid:cerebrospinal fluid, Humans, Hydroxyindoleacetic Acid:cerebrospinal fluid, Male, Middle Ag.   

: In this study we investigated the cerebrospinal fluid (CSF) concentrations of 5-hydroxyindoleacetic acid (5-HIAA) and homovanillic acid (HVA) in Alzheimer (AD) patients (n=75), patients with mild cognitive impairment (MCI, n=9) and patients with depression (n=7). CSF HVA was significantly elevated in AD with depression (Geriatric Depression Scale, 15 point version GDS>5) in comparison to AD without depression (p<0.05, ANOVA) and CSF HVA showed a significant positive correlation with the GDS score of AD-patients (p=0.03, Spearman Rho: 0.38, Spearman Rank Correlation). In the group of AD patients CSF 5-HIAA was positively correlated with cerebrospinal fluid beta-amyloid 1-42 (Abeta42), p<0.05, Spearman Rho: 0.3, Spearman Rank Correlation, but not with CSF tau. Additionally, there was a significant positive correlation between cerebrospinal fluid 5-HIAA and HVA in the group of AD patients (p<0.0001, Rho: 0.47, Spearman Rank correlation). Neither 5-HIAA nor HVA in CSF could differentiate between mild cognitive impairment, depression and AD. The results of this study support the hypothesis that the serotonergic system plays a role in the course of AD. They further suggest an important role of dopamine metabolism in depression within AD patients....

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Journal Article 2003; 24(1-2): 46-49 PubMed PMID: 12743531 Citation  Keywords:  Animals, Baclofen:pharmacology, Catecholamines:metabolism, Dopamine:metabolism, Female, GABA Agonists:pharmacology, Hypothalamus:growth & development, Muscimol:pharmacology, Norepinephrine:metabolism, Rats, Rats, Wistar, Receptors, GABA-A:drug effects, Re.   

OBJECTIVES: The aim of the present investigation was to determine whether the catecholaminergic system is involved in gabaergic and serotoninergic effects on gonadotrophin secretion during sexual development. To this end, we studied the effect of GABAergic and serotoninergic systems on hypothalamic catecholamine content at different stages of sexual development.

METHODS: The effect of GABA A and GABA B agonists and 5-hydroxy-L-tryptophan on hypothalamic noradrenaline and dopamine content were determined in prepubertal (16 days old) and peripubertal (30 days old) rats.

RESULTS: At 16 days of age GABA agonists did not modify hypothalamic noradrenaline content, whereas a significant decrease in catecholamine concentration was observed in peripubertal rats at 30 days of age. Similar changes were observed with GABA agonists administration on dopamine hypothalamic levels, i.e no effects at 15 days of age and a significant decrease at 30 days. The administration of 5-hydroxy-l-tryptophan (5-HTP) induced a decrease of hypothalamic concentration of noradrenaline and dopamine at both ages.

CONCLUSION: Results indicate that the GABAergic system modifies the hypothalamic catecholamine content in peripubertal but not in prepubertal rats while serotonin has an inhibitory effect at both stages of sexual maturation. Even though both systems induce similar ontogenic modifications on the gonadotrophin axis (stimulatory effect in prepubertal and inhibitory action in peripubertal and adult rats) the present results appear to indicate that GABAergic and serotoninergic systems regulate gonadotrophin secretion by different hypothalamic mechanisms....

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