Monday, 16 December 2013

The Effects of Hormone Catecholamines - Dopamine(2)

 Catecholamines, derived from the amino acid tyrosine, produced by the adrenal glands, which are found on top of the kidneys. are epinephrine (adrenaline), norepinephrine (noradrenaline) and dopamine. The hormone are released into the blood during times of physical or emotional stress.
9. Dopamine and motivation
Dopamine (DA) D2 receptors expressed in DA neurons (D2 autoreceptors) exert a negative feedback regulation that reduces DA neuron firing, DA synthesis and DA release. According to the mice study by Consejo Nacional de Investigaciones Científicas y Técnicas, midbrain DA neurons from mice deficient in D2 autoreceptors (Drd2(loxP/loxP); Dat(+/IRES-cre), referred to as autoDrd2KO mice) lacked DA-mediated somatodendritic synaptic responses and inhibition of DA release. AutoDrd2KO mice displayed elevated DA synthesis and release, hyperlocomotion and supersensitivity to the psychomotor effects of cocaine. The mice also exhibited increased place preference for cocaine and enhanced motivation for food reward. Our results highlight the importance of D2 autoreceptors in the regulation of DA neurotransmission and demonstrate that D2 autoreceptors are important for normal motor function, food-seeking behavior, and sensitivity to the locomotor and rewarding properties of cocaine(9).

10. Dopimine in punishment and reward
In the study of Variations of extracellular dopamine (DA(ext)) levels in prefrontal cortex were assessed by in vivo microdialysis, found that a benzodiazepine-sensitive activation of mesoprefrontal DA neurones is induced by exposure to novel stressful surroundings and by food availability and consumption. The fact that cortical DA(ext) levels remained unchanged in rats that exerted complete control upon negative stimuli indicates that an activation of the mesoprefrontal DA system is not required for punishment-induced behavioural blockade(10).

11. Dopamine and the inhibition of prolactin production
Transcription of the prolactin gene is dynamically controlled by positive and negative hormone signals that target the regulatory promoter region. According to the study by University of Toronto, dopamine D2 receptor activation and inhibition of MAPK (ERK1/2) signaling lead to rapid deacetylation of histones at the genomic prolactin promoter. Recruitment of specific HDAC/ corepressor complexes may be an important mechanism for repression of target gene transcription by Gi/o-coupled receptors(11).

12. Dopamine and sleep behaviour disorder (IRBD)
 In a prospective study, 20 patients with IRBD (mean age 70·55 years [SD 6·02]) underwent serial DAT imaging with (123)I-2β-carbomethoxy-3β-(4-iodophenyl)-N-(3-fluoropropyl)-nortropane ((123)I-FP-CIT) SPECT at baseline and again after 1·5 years and 3 years; 20 age-matched and sex-matched control participants (69·50 years [6·77]) underwent imaging at baseline and 3 years, showed that in patients with  sleep behaviour disorder (IRBD), serial (123)I-FP-CIT SPECT shows decline in striatal tracer uptake that reflects progressive nigrostriatal dopaminergic dysfunction. Serial (123)I-FP-CIT SPECT can be used to monitor the progression of nigrostriatal deficits in patients with IRBD, and could be useful in studies of potential disease-modifying compounds in these patients(12).

13. Dopamine in depression
According to the study by New York State Psychiatric Institute, clinical evidence includes alterations in depressive symptoms with aging (concomitant with possible changes in dopamine metabolism), potential dopaminergic involvement in several subtypes of depression, similarities between some of the symptoms of Parkinson's disease and those of depression (including psychomotor retardation and diminished motivation), and potential dopaminergic abnormalities in seasonal mood disorder. The biochemical evidence in patients with depression derives from studies of homovanillic acid, a dopamine metabolite, indicating diminished dopamine turnover(13).

14. Dopamine and Mood disorder
Dysfunction in the monoamine systems of serotonin (5-HT), norepinephrine (NE) and dopamine (DA) may causally be related to major depressive disorder (MDD). According to the study by University of Amsterdam,  monoamine depletion studies demonstrate decreased mood in subjects with a family history of MDD and in drug-free patients with MDD in remission, but do not decrease mood in healthy humans. Although depletion studies usefully investigate the etiological link of 5-HT and NE with MDD, they fail to demonstrate a causal relation. They presumably clarify a vulnerability trait to become depressed. Directions for further investigation of this vulnerability trait are proposed(14).

15. Dopamine in the regulation of cognition and attention
Dopamine (DA) acts as a key neurotransmitter in the brain.. In the early stages of Parkinson's disease (PD), alterations of executive functions also suggest a role for DA in regulating cognitive functions. Some other diseases, which can also involve DA dysfunction, such as schizophrenia or attention deficit hyperactivity disorder (ADHD) in children, as shown from the ameliorative action of dopaminergic antagonists and agonists, respectively, also show alteration of cognitive functions. According to the study by Université de La Méditerranée, a correlation exists between DA innervation and expression of cognitive capacities. Altering the dopaminergic transmission could, therefore, contribute to cognitive impairment(15).

16. Dopamine and working memory
There is accumulating evidence that training working memory (WM) leads to beneficial effects in tasks that were not trained. According to the study by Department of Neuroscience and Stockholm Brain Institute, Karolinska Institutet, variation in the dopamine transporter gene (DAT1) influences improvements in WM and fluid intelligence in preschool-age children following cognitive training. Our results emphasize the importance of the role of dopamine in determining cognitive plasticity(16).

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