Dopamine - Wikipedia
This difference was particularly clear in the hypothalamus but not present at all in Dopamine-beta-hydroxylase activity in the hypothalamus of rats treated for four Reserpine/pharmacology; Serotonin/metabolism; Tyrosine/pharmacology. Anatomical relationships of serotoninergic and noradrenalinergic projections with the GnRH system in septum and hypothalamus. Authors GnRH Serotonin Dopamine-β-hydroxylase Immunohistochemistry Rat brain. Dopamine is an organic chemical of the catecholamine and phenethylamine families that plays .. The posterior hypothalamus has dopamine neurons that project to the spinal cord, . or be converted to norepinephrine by the enzyme dopamine beta hydroxylase, . Association networks in the brain are greatly interlinked.
Schematic drawing illustrating association between serotonergic cell populations with GnRH and kisspeptin neurons in the brain of teleosts. There are multiple serotonergic 5-HT cell populations that express either Tph1 area shaded with yellow or Tph2 area shaded with green.
The organization of serotonergic projections were adopted from Lillesaar and Gaspar and Lillesaar Serotonin Receptors In teleosts, serotonin receptors have been identified and characterized in several species such as zebrafish, European flounder Platichthys flesusGulf toadfish Opsanus betaand puffer fish Yamaguchi and Brenner, ; Lu et al.
Additionally, in silico analysis have predicted gene sequences encoding serotonin receptors in several other species such as the tilapia Oreochromis niloticuscichlid fish Haplochromis burtonisouthern platyfish Xiphophorus maculatusand rainbow trout Oncorhynchus mykiss. In the brain of zebrafish, 5-HTr1aa and 5-HTr1ab are mainly expressed in the preoptic area and hypothalamus, and 5-HTr1bd is expressed in the hypothalamus Norton et al.
In the Gulf toadfish, 5-HT2A is widely expressed in the brain including the telencephalon, midbrain, cerebellum, hindbrain and in the pituitary Mager et al. In the zebrafish, 5-HT2C is expressed in the telencephalon, diencephalon, rhombencephalon, and spinal cord Schneider et al. Serotonin receptors are also expressed in peripheral tissues including gonadal tissues in teleosts. In the zebrafish, 5-HT2C receptor gene is expressed in the ovary Schneider et al.
In the toadfish, 5-HT2A is expressed in the ovary and testes Mager et al. Serotonin in Teleost Reproduction GnRH Release Serotonin modulates fish reproductive function via multiple pathways including through central preoptic-hypothalamic area and pituitary and peripheral gonads actions. In the hypothalamus, GnRH neurons play major role in the control of vertebrate reproduction.
Immunohistochemical study in the Atlantic croaker have demonstrated close association of serotonin fibers with olfactory bulbular and hypothalamic GnRH neurons Khan and Thomas, Indeed, serotonin stimulates GnRH release from the hypothalamus of the seabream and goldfish Yu et al. In the zebrafish, expression of serotonin receptors are seen in several brain regions containing GnRH neurons Norton et al.
However, no report has described the involvement of serotonin in the regulation of the kisspeptin system in any vertebrates to date. Gonadotropin Release In Atlantic croaker increasing serotonin concentrations are associated with levels of gonadotropin release from the pituitary Khan and Thomas, In several teleost species, serotonin stimulates release of gonadotropin in vivo and in vitro Somoza et al.
In vitro and in vivo studies in teleosts have shown the involvement of 5-HT1 or 5-HT1 receptor subtypes in stimulating gonadotropin secretion Somoza and Peter, ; Khan and Thomas, ; Wong et al.
These studies suggest that serotonin plays a prominent role in gonadotropin secretion in teleosts as demonstrated in mammals. In the goldfish, serotonin stimulates release of GnRH from the cultured brain preoptic-anterior hypothalamic region and pituitary fragments Yu et al. However, a recent in vivo study in Prussian carp Carassius gibelio Bloch demonstrated that serotonin alone had no influence on the spontaneous LH release, but the additive effects of serotonin was observed when GnRH analog was co-administered Sokolowska-Mikolajczyk et al.
These observations indicate functional interaction between serotonin and GnRH system in teleosts. However, an in vitro study in the red seabream demonstrated that serotonin stimulates the release of GnRH from the hypothalamus but not from the pituitary of immature fish Senthilkumaran et al.
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Therefore, in teleosts, the mode of action of serotonin on gonadotropin release could be changed reproductive-stage dependently. Additionally, serotonin is also known to modulate growth hormone GH release in goldfish Somoza and Peter, ; Wong et al. Those signaling pathways could also be involved in GnRH-primed gonadotropin secretion in teleosts.
Gonadal Maturation In addition to its central action on the reproductive axis, serotonin directly acts on gonads. In the Gulf killifish Fundulus grandis10 days of daily injection of serotonin precursor with dopamine precursor increases gonadosomatic index in male Emata et al. An in vitro study in the Japanese medaka Oryzias latipes has shown stimulatory effect of serotonin on oocyte maturation in a dose-dependent manner, which is modulated via stimulation of the synthesis of estrogen and the maturation-inducing steroids MIS: Although the expression of serotonin receptors in the testis has not been reported in teleosts, in freshwater catfish Channa punctatus BlochMAO activity has been noted in the testis Katti and Sathyanesan,and MOA activity and serotonin contents in testis represents correlative changes with testicular maturation Joshi and Sathyanesan, These results suggest that locally produced serotonin may participate in testicular maturation.
Social and Reproductive Behaviors The role of serotonin in social behavior has been well demonstrated in fish Winberg and Nilsson,while no report has demonstrated the involvement of serotonin in sexual behavior. As social status and reproductive activity are closely related, alteration of serotonin during different social status may directly influence reproductive activities.
In teleosts fish, serotonin plays primary inhibitory role in aggressive behavior Munro, ; Adams et al. In the fighting fish Betta splendens, serotonin decreases aggression via 5-HT1A receptors Clotfelter et al. On the contrary, higher levels of serotonin metabolite are found in the brain of subordinate compared with dominant fish Winberg and Lepage, ; Lorenzi et al. In a cichlid fish Astatotilapia burtoni, subordinate males have higher serotonergic turnover and higher expression of two serotonin receptor genes 5-HT1A and 2A in the telencephalon Loveland et al.
In the Arctic charr Salvelinus alpinus L. Modulation of Serotonin Activity Gonadal Steroids In teleosts, serotonin levels in the brain and pituitary are modulated by reproductive cycles and gonadal steroids Subhedar et al. In the tilapia, estrogen alters the brain serotonin content during the early brain development stage, which is mediated by decreasing TPH activity and increasing MAO activity Tsai and Wang, In the adult male marine yellow snapper Lutjanus argentiventrisserotonin levels in the telencephalon reach the peak during the prespawning period, and are lowest during the spawning period Hernandez-Rauda and Aldegunde, a.
Furthermore, blocking serotonin synthesis alters brain aromatase activity during the critical period of sexual differentiation in the tilapia Tsai et al. Some of these endocrine disruptors have a significant influence on fish reproductive function through the serotonin system. These results suggest that the serotonin system is one of the major targets for neuroendocrine disruption, which may lead to inhibition of reproductive functions.
Environmental and Social Factors In teleosts, the brain serotonergic activity displays diurnal or seasonal variations Khan and Joy, ; Senthilkumaran and Joy,which may have significant effects on the reproductive functions.
In teleosts, serotonin concentrations in the brain are higher in the morning than evening Fingerman, ; Khan and Joy, In the Channa punctatus, there are diurnal variations in the serotonin content Khan and Joy, as well as MAO activity in the hypothalamus Khan and Joy, suggesting diurnal variation of the hypothalamic serotonin levels.
Seasonal variation of hypothalamic serotonin content has also been noted in the catfish, Heteropneustes fossilis Senthilkumaran and Joy, These seasonal changes in serotonin levels could also be due to environmental factors such as water temperature and photoperiod.
In the tilapia, the hypothalamic serotonin content is lower in fish exposed to higher water temperature than those in lower temperature group Tsai and Wang, In contrast, expression of serotonin receptors 5-HT1A and 1D in the brain are increased by low temperature in the tilapia during the sexual differentiation Wang and Tsai, In several fish species, photoperiods alter hypothalamic serotonin content and turnover Olcese et al.
In the goldfish, pinealectomy and melatonin administration have a significant effect on hypothalamic serotonin content and serotonergic activity Olcese et al. These results indicate environmental factors may influence reproductive functions via diurnal and seasonal change of serotonin activity.
In the protogynous fish, Hawaiian saddleback wrasse Thalassoma duperreyserotonin inhibits both initiation and completion of sex reversal Larson et al. Furthermore, in the same fish, serotonin levels in the brain are altered by socially induced sex reversal, which could be associated with territorial acquisition Larson et al.
These results suggest that serotonin is also regulated by social behaviors. SSRIs have been detected as pharmaceutical contaminants in surface waters and sewage effluents Kreke and Dietrich, ; Oakes et al. SSRIs block the presynaptic SERT and prevent the clearance of synaptic serotonin, which causes an elevation of extracellular serotonin concentrations Tollefson and Rosenbaum, In female fish, fluoxetine treatment significantly reduces egg production and ovarian levels of estrogen, and gene expression levels of aromatase, FSH- and LH-receptors Lister et al.
The cholinergic signal is terminated by the serine hydrolase acetylcholine esterase AChE bound to the postsynaptic membrane. The hydrolysis produces choline, which is taken up by the presynaptic neuron and recycled, and acetate. The catalytic activity of AChE depends primarily on three amino acid residues — serine, histidine and glutamate a similar triad exists also in serine proteases with aspartate instead of glutamate.
The hydroxyl group of serine attacks the ester bond. AChE is not entirely specific for ACh, it also hydrolyses other choline esters. Cholinergic signalling in the nervous system is mediate by two receptor types with several subtypes: The response of the postsynaptic neuron is thus relatively slow. So far five subtypes of muscarinic receptors have been identified. This receptor mediates an excitatory response via a Gq protein starting a signalling cascade leading to a decreased permeability for potassium.
It is thought that a decrease in their function or density is one of the causes of dementia. They mediate an inhibitory response via a Gi protein, which activates potassium channels via its beta-gamma subunit dimer thus causing membrane hyperpolarization. This is the mechanism by which the vagus nerve exerts its negative chronotropic effect on the sinoatrial node and the negative dromotropic effect on the atrioventricular node.
In the CNS M2 receptors act as autoreceptors on presynaptic neurons mediating negative feedback inhibition in the cortex and the hippocampal formation. Although they exist in the CNS at a relatively low density they can induce a potent emetic effect.
The effect of ACh on blood vessels is worth pointing out. While ACh can cause smooth muscle contraction in blood vessels it causes vasodilation. This is not a direct effect on the smooth muscle but rather a heterotropic inhibition of noradrenergic sympathetic activity and the stimulation of NO production in the endothelium. M3 receptors are being intensively studied due to their role in the development of type 2 diabetes.
In the CNS they are expressed in areas responsible for the monitoring and regulation of blood glucose levels, i. In the pancreas they are expressed in beta-cells of the islets of Langerhans, which explains why certain antipsychotic agents used to treat schizophrenia may cause blood glucose dysregulation and increase the risk of T2D via blocking M3 receptors. They are found mainly in the striatum, where they function mainly as regulatory autoreceptors on cholinergic neurons the same role as M2 receptors in the hippocampus and other cortical regions.
In the striatum M4 receptors attenuate the activity of excitatory D1 receptors, through which dopamine increases the activity of the extrapyramidal motor system.
The physiological implications of this interaction are unclear. Most studies on M5 receptors to date were performed in vitro. The basic division is into a muscular type NM receptor present mostly in the neuromuscular junction and a neuronal type NM found in all postsynaptic terminals in autonomic ganglia.
They increase the permeability for calcium and increase the amount of released neurotransmitters. Cholinergic neurons are found mainly in the basal nucleus of Meynert and in septal nuclei. These neurons project into the cortex and the hippocampus. They play a role in the activation of certain cortical areas and in short term memory consolidation.
These affect arousal, sleep cycle and are important for the initiation of the REM sleep phase. There are cholinergic interneurons in the striatum, which form a part of the basal ganglia circuit and thus play a role in the regulation of posture, movement initiation and selection of appropriate movement patterns.
Some are highly toxic substances such as extremely effective organophosphates. These compounds form a strong covalent bond with the OH group of the serine residue in the active site of the enzyme, which lasts for weeks. Organophosphates are mostly used as insecticides and as such can cause accidental intoxications. There are also highly toxic volatile organophosphates used as nerve gases such as sarin, tabun and VX. In this chapter we will mostly cover the functions of the noradrenergic and dopaminergic systems.
Synthesis and inactivation of catecholamines All catecholamines are derived from the aromatic amino acid L-tyrosine or from phenylalanine via tyrosine.
4. Neurotransmitter Systems • Functions of Cells and Human Body
Their structure contains a catechol ring — benzene ring with two hydroxyl groups — with a side chain containing an amino group. The conversion of tyrosine to adrenaline occurs in the following steps: The reaction is catalysed by tyrosine hydroxylase, the rate limiting enzyme for catecholamine synthesis.
The main regulatory mechanism is feedback inhibition by catecholamines. This reaction is catalysed by DOPA decarboxylase a. Alpha-methyldopa, is a competitive inhibitor of DOPA decarboxylase and is used to treat hypertension. This reaction is catalysed by phenylethanolamine-N-methyltransferase PNMT with S-adenosylmethionine as its co-substrate and methyl group donor.
The activity of this enzyme is positively regulated by glucocorticoids cortisol formed in the adrenal cortex and transported into the medulla via the suprarenal portal system.
The catecholamine signal is terminated by the re-uptake of the neurotransmitter and subsequent intracellular inactivation. The two enzymes catalysing this inactivation are: This sequence is responsible for the following transformations: It is a flavoprotein — contains a covalently bound FAD.
Vanillylmandelic acid is excreted mainly in the urine and its excretion can be used to estimate the production of catecholamines in the organism. It is mainly used when an adrenal medulla tumor pheochromocytoma is suspected. Noradrenergic system Noradrenaline in the CNS mainly regulates the activity of other neurotransmitter systems. Noradrenergic pathways increase or decrease the excitability of target areas depending on the receptors expressed and other poorly understood mechanisms.