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Complex interactions between the brain and peripheral tissues mediate the effective control of energy balance and body weight. Hypothalamic and hindbrain neural circuits integrate peripheral signals informing the nutritional status of the animal and in response regulate nutrient intake and energy utilization. Obesity and its many medical complications emerge from the dysregulation of energy homeostasis. Excessive weight gain might also arise from alterations in reward systems of the brain that drive consumption of calorie dense, palatable foods in the absence of an energy requirement. Several neurotrophins, most notably brain-derived neurotrophic factor, have been implicated in the molecular and cellular processes underlying body weight regulation. Here, we review investigations interrogating their roles in energy balance and reward centers of the brain impacting feeding behavior and energy expenditure. [ABSTRACT FROM AUTHOR]

Hepatic circulation is considered to be a low-resistance system, which accommodates about 30% of the total cardiac output. Like pulmonary circulation, mammalian liver also gets dual blood supply, from both portal vein and hepatic artery. [ABSTRACT FROM AUTHOR]

This chapter describes recent developments in the analysis of kappa opioid receptor (KOR) function at a molecular, cellular and systems level within the central and peripheral nervous system. A combination of neuroanatomical, electrophysiological and behavioral techniques have been used to probe the functional consequences of KOR activation in the brain and spinal cord in both normal and pathological conditions. As a result of a number of studies conducted over the last three decades it is apparent that kappa opioid receptors will emerge as an important therapeutic target for both psychiatric and neurological pathologies. The following chapter reviews where the field has been, but importantly discusses gaps in our knowledge and highlights important new directions for the future. [ABSTRACT FROM AUTHOR]

Oxidative (OS) and nitrative stress are thought to be major factors in the generation and maintenance of neurodegeneration in Parkinson΄s disease (PD). Generation and maintenance of the parkinsonian state may involve separate mechanisms or may be interrelated, because neurodegeneration in this disease condition usually starts late in life and continues at an accelerated rate, although some forms of PD resulting from gene mutations may appear early in life. In this review we present the major recent findings connecting OS and PD, but also review in brief the relevant physiological and pathological findings in PD for the uninitiated. The major enzyme systems connected with OS generation with possible relevance to PD are discussed, as well as available antioxidants. A major contention in the past has been that oxidative metabolism of dopamine by MAO creates a potentially damaging environment for the dopaminergic neuron, by production of hydrogen peroxide which in the presence of reactive iron can be further metabolized to reactive oxygen species by Fenton chemistry. We review here the factors controlling iron levels in the brain, in particular the emerging role of neuromelanin, and the possible interventions available. Recent findings based on staged appearance of synucleinopathy show that Lewy bodies appear initially in peripheral structures and migrate via connecting neuronal tracts to finally reside in upper brain areas. These findings have been interpreted as showing the involvement of an infective agent in PD, which, if true, introduces an additional factor to the simplified hypotheses based on dopamine turnover-induced OS. The recent demonstration of clinical neuroprotective action in PD of the MAO-B inhibitor rasagiline may provide support for the OS hypothesis, but on the other hand, alternative explanations for this finding are also available. We can anticipate much further activity in the direction of new therapeutics to control OS in PD as well as in other related conditions. [ABSTRACT FROM AUTHOR]

Sexual experience is a significant modulator of behaviour in male rodents, inducing mating behaviour changes, increased sexual motivation and olfactory learning. Sexually experienced males exhibit greater motivation to investigate females and show preferences for receptive oestrous females and their odours which are not seen in virgins. These behavioural effects of sexual experience are accompanied by neurobiological changes affecting forebrain sensitivity to steroid hormones, mesolimbic dopamine function and neural activity in the basal hypothalamus and olfactory pathways. These changes suggest that sexually experienced males are better able to detect receptive females, are more motivated to pursue them and are more proficient copulators. Furthermore, this response to sexual experience appears to be mediated by imprinted genes. Imprinted genes are a small class of mammalian autosomal genes that are expressed in parent-of-origin fashion and which are key regulators of placentation and development in mammals. Mice carrying a knockout of the paternally expressed gene Peg3 have deficits in maternal care and offspring development, but Peg3 mutant males also fail to show any sexual experience-dependent changes in behaviour or learned olfactory preferences. There are also no changes in female odour-evoked neural activity in the hypothalamus, vomeronasal system or main olfactory pathway of Peg3 mutants after sexual experience, suggesting a deficit in sexual experience-dependent forebrain plasticity. Peg3 appears to regulate male behavioural traits that would enhance its own transmission down the male line, suggesting that this imprinted gene has evolved to directly influence plasticity in male reproductive behaviour. [ABSTRACT FROM AUTHOR]

Among the most important neurodegenerative disorders affecting aging adults around the world are Alzheimer΄s disease (AD), which affects around 4.5 million people in the United States, and Parkinson΄s disease (PD), which has a prevalence of about 160 cases per 100,000 people and an incidence of about 20 cases per 100,000 people per year. In both disorders prevalence and incidence increase with age. AD is the main dementing disorder, whereas cognitive dysfunction and dementia eventually occur in 20–40% of patients with PD. In this chapter the neurobiology of these diseases is reviewed. Classical, anatomically defined local circuits are summarized. Data obtained using advanced imaging techniques, such as SPECT, and functional MRI, and electrophysiological recordings, are highlighted. The main emphasis for both PD and AD is on cognitive deficits from the perspective of brain circuits and synaptic physiological abnormalities as well as on their biochemical correlates. In particular, among nonmotor defects in Parkinson΄s disease sensory deficits are also emphasized in relation to visuocogntive and attentive dysfunction. The main neurotransmitter systems involved are dopamine (in PD) and acetylcholine (both in PD and AD). The logic role of dopamine in the retinal circuitry is discussed in relation to sensory (visual) dysfunction in PD. The contribution of neurotransmitter/modulators beyond the dopaminergic and cholinergic systems in the basal ganglia and in several cortical areas is reviewed. This involves glutamate, adenosine, and GABA. The cognitive effect of genetic variability of catechol-o-methyltranferase, in the prefrontal cortex is summarized. Although advances in the understanding of AD and PD pathophysiology have been significant, fundamental issues remain unsolved. The powerful neuropathological arguments concerning the progression of PD based on alpha synuclein predict late involvement of cortical circuits, presumably responsible for cognitive changes. The role of acetylcholine and diverse cholinergic receptors in cognitive dysfunction in both AD and PD will need further studies. Future studies may potentially lead to a bridging theory of cognitive impairment in both AD and PD. [ABSTRACT FROM AUTHOR]

Bipolar disorder (BPD) is a major medical and social burden, but little is known about the specific pathophysiology of BPD. The key biogenic amines in the aminergic system include serotonin (5-HT), norepinephrine (NE), dopamine (DA), and acetylcholine (ACh). By analyzing these neurotransmitters, this chapter highlights three hypotheses in the pathophysiology of BPD: the biogenic amine hypothesis, the cholinergic–aminergic balance hypothesis, and the permissive hypothesis. Evidence from select studies of cerebrospinal fluid, postmortem subjects, neuroimaging, genetic factors, and pharmacological agents will be used to reconcile these hypotheses. Possible explanations for discrepancies in these hypotheses are given, and directions for future studies are suggested. [ABSTRACT FROM AUTHOR]

Data suggest that low levels of dopamine D2 receptors and attenuated responsivity of dopamine-target regions to food intake is associated with increased eating and elevated weight. There is also growing (although mixed) evidence that genotypes that appear to lead to reduced dopamine signaling (e.g., DRD2, DRD4, and DAT) and certain appetite-related hormones and peptides (e.g., ghrelin, orexin A, leptin) moderate the relation between dopamine signaling, overeating, and obesity. This chapter reviews findings from studies that have investigated the relation between dopamine functioning and food intake and how certain genotypes and appetite-related hormones and peptides affect this relation. [ABSTRACT FROM AUTHOR]

The neurobiology of eating disorders (EDs) is largely unknown. However, brain imaging studies over the past decade have identified neurotransmitter alterations that could be part of dysfunctional behavior characteristics of EDs. In this chapter we focus on a specific behavioral construct, the brain reward system, and demonstrate a functional brain imaging approach toward identifying dopamine function in anorexia nervosa (AN). We demonstrate how human brain reward activation can be used in a translational approach to test whether computer models, based on basic science research, can predict expected in vivo reward system activation, and how such an approach can identify specific biologic alterations in a psychiatric population. [ABSTRACT FROM AUTHOR]

Hyperactivity in anorexia nervosa is difficult to control and negatively impacts outcome. Hyperactivity is a key driving force to starvation in an animal model named activity-based anorexia (ABA). Recent research has started unraveling what mechanisms underlie this hyperactivity. Besides a general increase in locomotor activity that may be an expression of foraging behavior and involves frontal brain regions, the increased locomotor activity expressed before food is presented (food anticipatory behavior or FAA) involves hypothalamic neural circuits. Ghrelin plays a role in FAA, whereas decreased leptin signaling is involved in both aspects of increased locomotor activity. We hypothesize that increased ghrelin and decreased leptin signaling drive the activity of dopamine neurons in the ventral tegmental area. In anorexia nervosa patients, this altered activity of the dopamine system may be involved not only in hyperactivity but also in aberrant cognitive processing related to food. [ABSTRACT FROM AUTHOR]

An important goal for alcohol dependence treatment research is the identification of personal characteristics that can be used to select the treatment regimen that will have the greatest probability of success. Such personalized treatment for alcohol dependence is not yet a reality. Individual differences in the genetic architecture that underlie the etiology of alcoholism and of the pharmacogenetics of medications used in alcoholism treatment are likely to be important in the development of personalized treatment. In 2000, Johnson proposed a mechanistic model of the contribution to differential response to pharmacological alcoholism treatment of a well-studied, common genetic polymorphism in the regulatory region of the gene that codes for the serotonin transporter (5-HTTLPR). This Johnson Model contained many parameters and proposed multiple interactions, which made predictions difficult to make, but also made it a good candidate for modeling with a dynamic systems-based model. This chapter describes personalized alcoholism treatment and pharmacogenetics, and discusses the Johnson Model and a dynamic systems model as well as the potential for using such models for investigating personalized alcoholism treatment. [ABSTRACT FROM AUTHOR]

Drugs of abuse interact with brain circuitry involved in reward and reinforcement, and it is thought that through these interactions drugs can gain influence over brain function, leading to maladaptive behavior. This chapter reviews the basic concepts of reward and reinforcement, with particular emphasis on positive and negative reinforcement and the differences between goal-directed and stimulus-driven ˵habitual″ behavior. The role of particular neurotransmitters and neural circuitry, most notably cortico-basal ganglia circuits, in reward, reinforcement, and drug addiction is then discussed. Several laboratory animal models of drug use are considered along with critical consideration of what constitutes an adequate ˵addiction″ model. The actions of addictive drugs within the brain reinforcement and reward circuitry are then reviewed, including information about the molecular targets of abused drugs, their actions on relevant circuitry, and their actions in the aforementioned laboratory animal models. Finally, the neurobiological underpinnings of drug use, abuse, and addiction are discussed, and some ideas are put forward about future research in this field. [ABSTRACT FROM AUTHOR]

Renalase, a novel, secreted flavin-adenine-dinucleotidedependent amine oxidase regulates cardiac function and blood pressure. The enzyme is rapidly activated in plasma by either modest increases in blood pressure or catecholamines. Protein expression in kidney and heart and its activation in plasma are markedly reduced in chronic kidney disease. The renalase knockout mouse is mildly hypertensive and more likely to develop severe ischemic renal and cardiac injury. Administration of recombinant renalase protects against myocardial injury and improves cardiac function. Preliminary data suggest that renalase may serve as an early biomarker for acute kidney injury. Single nucleotide polymorphisms of the renalase gene are reported to be associated with essential hypertension and more severe cardiovascular complications. The molecular mechanisms that underlie renalase΄s action and its therapeutic utility are being examined. [ABSTRACT FROM AUTHOR]

Chapter 22 of the book "Ultimate Review for the Neurology Boards, Second Edition," by Drs. Hubert H. Fernandez, Stephan Eisenschenk and Michael S. Okun is presented. It discusses adult psychiatry in relation to psychochemistry, psychiatric illnesses, and medical ethics. It cites dopamine, serotonin and norepinephrine as neurotransmitters.

Control of mean arterial blood pressure and cardiac output is highly desirable in certain operative procedures and in post cardiac operation. This paper emphasizes on a fuzzy controller to control these two variables within the present limits by administering three drugs dopamine, Sodium Nitro Prusside and Phenylephrine which perform the function of increasing heartbeat rate, decreases, increases blood pressure respectively. A fuzzy PD controller with 25 rules is designed to achieve this, which controls the drug delivery unit. This work makes use of few mathematical models whose response to these three drugs mimics the human cardiovascular system. This work can be extended by ASIC Fuzzy control system, which is capable of modeling the cardiovascular mechanism. Till now the usual procedure is that the clinical personal (anesthesio logist) will monitor the changes and will accordingly adjust the infusion rates. The main goals of general anesthesia are adequate hypnosis, analgesia and maintenance of vital functions. For some special kinds of operations neuromuscular block is essential. Furthermore the patient safety and cost reduction as a case of minimized drug consumption and shortened postoperative recovery phases are part of the main issues to motivate automation in anesthesia. Since the beginning of the eighties engineers and physician are working together in the field of the development of closed-loop systems for drug delivery. The work gives a short overview about the development of the automation in drug delivery systems over the last years without the claim of completeness and expressed the much more vision. [ABSTRACT FROM AUTHOR]

Juvenile hormone (JH) and ecdysteroids play a gonadotropic role in insect reproduction. For the normal progress of oogenesis, a proper balance between JH and 20-hydroxyecdysone (20E) is of a paramount importance. An imbalance of gonadotropins (shifting the balance either to the side of JH or 20E) leads to reproductive defects: a rise in JH titre leads to oviposition arrest, a rise in 20E level, to the degradation of vitellogenic oocytes. Upon a change in the level of one of the gonado tropins as a result of a mutation, effect of a stressor or pharmacological agent, the balance is restored owing to the relative change in the titre of the other one. Mediators in the JH and 20E interrelationship are biogenic amines, dopamine and octopamine. Existence of the mechanism of gonadotropin's – reciprocal regulation is adaptive. [ABSTRACT FROM AUTHOR]

Classically, steroid hormones have been thought to mediate their actions by binding to intracellular proteins that migrate to the nucleus and induce changes in gene expression. However, it is now becoming clear that steroids may also induce rapid actions through the activation of various second messenger pathways by cell surface receptors. Considerable controversy exists over the mechanisms underlying these non-genomic effects. Thus, some effects may be attributable to the allosteric actions of steroids on ligand-gated ion channels. Other effects may be mediated via the activation of G-protein coupled second messenger pathways, including in a few cases the direct activation of specific G-protein coupled receptors (GPCRs). This chapter reviews the evidence for the non-genomic actions of ecdysteroids and parallels are drawn with the non-genomic actions of vertebrate steroids in a number of systems. Possible molecular mechanisms for non-genomic actions of steroids are discussed. These include the possible actions of steroids on nuclear receptors that migrate to the cell surface and also their actions on cell surface receptors including, GPCRs. Recent evidence for the actions of ecdysteroids on insect cell surface receptors, including a recently cloned Drosophila GPCR, DmDopEcR, is reviewed. The direction of future research in the area of non-genomic actions of ecdysteroids is considered. [ABSTRACT FROM AUTHOR]

Intercellular information transfer in the nervous system is mediated by chemical neurotransmitters. The fidelity of this process requires the rapid release and clearance of the neurotransmitter from the synaptic cleft. In addition to metabolic pathways for synthesis of neurotransmitters, two specific mechanisms, vesicular storage and local reuptake, have evolved to facilitate neurotransmission. These processes are mediated by transporter proteins: vesicular neurotransmitter transporters to fill the vesicles and plasma membrane neurotransmitter transporters to clear the synaptic cleft. This chapter discusses the synthesis, packaging, and recycling of the classic neurotransmitters with an emphasis on the transporter proteins that are integral to these pathways. [ABSTRACT FROM AUTHOR]

With the successful application of molecular genetic methods to the plant alkaloid field, we now have sophisticated tools at our disposal to study regulation of enzymatic biosynthesis, as well as determining the cellular and subcellular localization of these enzymes. The availability of ever-increasing numbers of recombinant enzymes has enabled thorough analyses of selected alkaloid biosynthetic enzymes at the biochemical and structural levels. We are just beginning to use this knowledge to metabolically engineer alkaloid metabolism in plants and in in vitro cultures. Multicellular compartmentation of alkaloid pathways must be considered if meaningful metabolic engineering experiments are to be designed; for example, we will need to use promoters that drive transgene expression in the correct cell types. Regulation of these pathways at the gene and enzyme level is complex and there is still much to be learned about metabolite levels, multienzyme complexes, and pathway interconnections, as we systematically overexpress and suppress gene transcription. Today, pathway engineering in plants remains highly variable. When we perturb cellular physiology, metabolite homeostasis and intra- and intercellular partitioning can be affected in unpredictable ways. Predictive metabolic engineering to generate plants with tailored alkaloid profiles for basic research and for commercial production is clearly a challenge for the future. [ABSTRACT FROM AUTHOR]

‘Unting is all that's worth living for – all time is lost wot is not spent in ‘unting – it is like the hair we breathe – if we have it not we die – it's the sport of kings. The most vital possessions of the plant are the chloroplasts in the cells of its leaves. Through these, the organism can convert, for its own purposes, a fraction of the solar energy that falls upon it. Sunlight is remarkably uniform in its intensity, and a plant has little to gain by moving about. It can thus afford a relatively stationary existence, the only motion being that required to reach regions beyond the shade of its immediate environment and its competitors. Because they have no chloroplast-bearing cells, animals have paid the penalty of having to develop several specialized functions in order to satisfy their energy requirements. They must have a means of locomotion and feeding, and some form of coordination of these faculties, however primitive, is needed. And as insurance against the unsuccessful forage, they should be able to store digested energy. Moreover, unless an animal is so small that the normal process of diffusion is adequate, it must have a circulatory system to distribute dissolved gases and chemical compounds to its various parts. [ABSTRACT FROM AUTHOR]

In this chapter the topic of inflammation in Parkinson΄s disease (PD) and in models of human disease will be reviewed. To set the stage, the biological, clinical and pathological hallmarks of PD and related degenerative conditions will be presented. A more comprehensive review of PD can be found in the following two references (Fahn and Przedborski, 2005; Dauer and Przedborski, 2003). [ABSTRACT FROM AUTHOR]

A novel brain inspired cognitive system architecture of an active visual search model is presented. The model is multi-modular consisting of spatial and object visual processing, attention, reinforcement learning, motor plan and motor execution modules. The novelty of the model lies on its decision making mechanisms. In contrast to previous models, decisions are made from the interplay of a winner-take-all mechanism in the spatial, object and motor salient maps between the resonated by top-down attention and bottom-up visual feature extraction and salient map formation selectively tuned by a reinforcement signal spatial, object and motor representations, and a reset mechanism due to inhibitory feedback input from the motor execution module to all other modules. The reset mechanism due to feedback inhibitory signals from the motor execution module to all other modules suppresses the last attended location from the saliency map and allows for the next gaze to be executed. [ABSTRACT FROM AUTHOR]

In the antisaccade task, subjects are instructed to look in the opposite direction of a visually presented stimulus. Controls can perform this task successfully with very few errors, whereas schizophrenia patients make more errors and their responses are slower and more variable. It has been proposed the fundamental cognitive dysfunction in schizophrenia involves prefrontal dopaminergic hypoactivity. We examine via computer simulations the effects of dopamine on the variability of aSRTs in a neural cortico-collicular accumulator model with stochastic climbing activity. We report the simulated aSRTs for the hypo-DA level have higher standard deviation and mean values than in the normal and hyper DA level. The simulated higher mean and standard deviation for the hypo-DA group resemble the performance differences in the antisaccade task observed in patients with schizophrenia and are in accordance with the theory of a hypo-DA state in the frontal cortical areas of patients with schizophrenia. [ABSTRACT FROM AUTHOR]

Three factor Isotropic sequence order (ISO3) learning is a form of differential Hebbian learning where a third factor switches on learning at relevant moments for example, after reward retreival. This switch enables learning only at specific moments and, thus, stablises the corresponding weights. The concept of using a third factor as a gating signal for learning at relevant moments has been extended in this paper to perform second order conditioning (SOC). We present a biological model of the sub-cortical nuclei of the limbic system that is capable of performing SOC in a food seeking task. The 3rd-factor is modelled by dopaminergic neurons of the VTA which are activated via a direct excitatory glutamatergic pathway, and an indirect dis-inhibitory GABAergic pathway. The latter generates an amplification in the number of tonically active DA neurons. This produces an increase in DA outside the event of a primary reward and enables SOC to be accomplished. [ABSTRACT FROM AUTHOR]

Posttraumatic stress disorder (PTSD) is a serious and devastating psychiatric illness that develops after an exposure to a terrifying event. PTSD is associated with a diminished quality of life and considerable emotional suffering in patients and their families, and can be a financial burden to the whole society. PTSD symptoms include preoccupation and re-experiencing of the traumatic event, fear, anxiety, arousal, sleep disturbances, nightmares, emotional numbness, withdrawal, terror, helplessness, horror, irritability and aggression, and the loss of the sense of basic safety. However, not all subjects exposed to a traumatic event will develop PTSD. Brain regions mediate the stress response via specific neurochemical circuitry, but in PTSD the copping mechanisms change from normal reactions to stress into maladaptive responses. The studies of the neurobiology of PTSD, which primarily involves the neuroendocrine dysregulation (of the activity of the hypothalamic-pituitary adrenal axis), dysfunction of the noradrenergic, serotonergic, dopaminergic, GABA-ergic, glutamatergic, and opioidergic neurotransmitter systems, and genetic polymorphisms, might improve the understanding and treatment of PTSD. A complex interaction between trauma and genetic and environmental factors, and early experiences, underlies the development of PTSD. The authors present a review of their own results related to biomarkers in Croatian war veterans with combat related PTSD. [ABSTRACT FROM AUTHOR]

Catecholamines are produced by the chromaffin tissue of the adrenal medulla. They also are found in sympathetic nerve endings and in the brain. The major catecholamines are epinephrine, norepinephrine, and dopamine. They prepare the body for the fight-or-flight stress response, help regulate metabolism, and are excreted from the body by the kidneys. Levels are affected by diurnal variations, fluctuating in response to stress, postural changes, diet, smoking, drugs, and temperature changes. As a result, blood measurement is not as reliable as a 24-hour timed urine test. For test results to be valid, all of the previously mentioned environmental variables must be controlled when the test is performed. Elevated homovanillic acid levels rule out pheochromocytoma because this tumor primarily secretes epinephrine. Elevated catecholamines without hypertension suggest neuroblastoma or ganglioneuroma. Findings should be compared with metanephrines and vanillylmandelic acid, which are the metabolites of epinephrine and norepinephrine. Findings should also be compared with homovanillic acid, which is the product of dopamine metabolism. [ABSTRACT FROM AUTHOR]

Catecholamines are produced by the chromaffin tissue of the adrenal medulla. They are also found in sympathetic nerve endings and in the brain. The major catecholamines are epinephrine, norepinephrine, and dopamine. They prepare the body for the fight-or-flight stress response, help regulate metabolism, and are excreted from the body by the kidneys. Catecholamine levels are affected by diurnal variations, fluctuating in response to stress, postural changes, diet, smoking, drugs, and temperature changes. As a result, blood measurement is not as reliable as a 24-hour timed urine test. Results are most reliable when the specimen is collected during a hypertensive episode. Catecholamines are measured when there is high suspicion of pheochromocytoma but urine results are normal or borderline. Findings should be compared with the metabolites of epinephrine and norepinephrine, metanephrines and vanillylmandelic acid, and with the product of dopamine metabolism, homovanillic acid. Use of a clonidine suppression test with measurement of plasma catecholamines may be requested. Failure to suppress production of catecholamines after administration of clonidine supports the diagnosis of pheochromocytoma. [ABSTRACT FROM AUTHOR]

Chapter 4 of the book "Neuroscience of Psychoactive Substance Use and Dependence" is presented. It explores the pharmacology and behavioral effects of different classes of psychoactive substances. It offers an overview of the major classes of these substances and their effects in the brain. It points that almost all psychoactive substances share the common property of increasing mesolimbic dopamine function.

The article presents an encyclopedia entry for "neurotransmitter transporters." The two major types of neurotransmitter transporters are vesicular transporters and plasma membrane transporters. Vesicular amine transporters are a gene family of transmembrane spanning domain antiporters that mediate the vesicular uptake of amine-containing neurotransmitters, such as dopamine and serotonin.

A definition of the term "dopamine system" is presented. It refers to the cellular and biochemical network that is involved in the synthesis, release and response to dopamine. Characteristics and basic mechanisms of the dopamine system are discussed. A diagram is presented that shows the process of dopamine synthesis and metabolism in humans.

Central pathways, neurochemistry, synaptic pharmacology and central functions of dopamine. Pathways: mapping by histofluorometric technique to show nigrostriatal and mesolimbic-cortical tracts from subcortical nuclei (A9, A10) and other minor pathways. Neurochemistry: the enzymes involved in synthesis and metabolism, drug effects on them and the toxins, 6-OHDA and MPTP. Receptors: evidence for the classification into two families (D1 and D5) and (D2 D3 D4), their structure, distribution, second messenger systems, synaptic effects (mostly inhibitory). The use of agonist drugs in Parkinsonism and antagonists in schizophrenia. Central functions: dopamine has an important role in the control of motor function, too little causing akinesia (Parkinson's disease) and too much giving dyskinesia. It is also involved in psychotic behaviour, reward and reinforcement. [ABSTRACT FROM PUBLISHER]

A monograph for the pharmaceutical substance DOPAMINI HYDROCHLORIDUM/DOPAMINE HYDROCHLORIDE" from the fourth edition of "The International Pharmacopoeia" is presented. Dopamine hydrochloride is categorized as a cardiovascular drug; sympathomimetic and described as colourless crystals or a white or almost white, odourless crystalline powder, that is freely soluble in water. It is recommended that this substance be kept in a well-closed container, protected from light. Procedures for performing an identity test and assay of the substance are described.

A definition of the term "tyrosine hydroxylase" (TH) is presented. It refers to an enzyme that catalyzes the hydroxylation of tyrosine to 3,4-dihydroxyphenylalanine in the brain and adrenal glands. TH is also the rate-limiting enzyme in the biosynthesis of dopamine. TH is a nonheme iron-dependent monoxygenase that needs the presence of the cofactor tetrahydrobiopterin.

A definition of the term "sensitization" is presented. It refers to the dramatic augmentation of behavioral and neurological responses associated with mesolimbic dopamine transmission that often develops with intermittent exposure to drugs of abuse. Its significance for drug abuse studies is evidenced by the notion that repeated drug use leads to a progressive and persistent hypersensitivity of neural systems that mediate incentive salience.

The article presents information on nucleus accumbens. The limbic system includes this part. Nucleus accumbens receives dopaminergic input through the mesolimbic system that originates from cell bodies in the ventral segmental area. Cocaine, amphetamine and opiates have been proven to increase the level of dopamine release in these neurons.

An encyclopedia entry for the term "mesolimbic system/reward system," is presented. A neurotransmitter system that is particularly sensitive to electrical self-stimulation is the mesolimbic dopamine projection that originates in the ventral tegmental area. It projects to structures closely associated with the limbic system, most prominently the nucleus accumbens shell region and the prefrontal cortex.

The article presents an encyclopedia entry for "L-DOPA/Levodopa." L-DOPA/Levodopa is the main drug used to treat Parkinson's disease. The immediate metabolic precursor to dopamine, L-DOPA or L-dihydroxphenylalanine is converted to the active neurotransmitter dopamine by the action of the enzyme aromatic amine acid decarboxylase.

A definition of the term "Dopamine-Β-hydroxylase" is presented, which refers to the element that synthesizes norepinephrine from dopamine.

A definition of the term "dopamine" is presented, which refers to a neurotransmitter in dopaminergic nerves.

A definition of catecholamines is presented. These are biogenic amines that have a catechol or o-dihydroxy-benzol structure. From tyrosine, catecholamines are synthesized in nerve endings. Catecholamines include dopamine, noradrenaline or norepinephrine, and adrenaline or epinephrine.