Dopamine in brain

Zarevics P, Seller PE (1979) Simultaneous rate-independent and rate-dependent assessment of intracranial self-stimulation evidence for the direct involvement of dopamine in brain reinforcement mechanisms. Brain Res 169 499-512. 

Cervo L, Rossi C, Samanin R The role of serotonin and dopamine in brain in the antidepressant-like effect of clonidine in the forced swimming test. Neuropharmacology 31 331-335, 1992... 

Methylphenidate is chemically and pharmacologically similar to amphetamine. Both act by releasing norepinephrine and dopamine in brain. Both produce increased mental activity with little action on central and peripheral functions. It is well absorbed orally, metabolized and excreted in urine. 

The problem with the silylation of different biogenic amines is that it is difficult to prepare uniform derivatives as these compounds usually contain amino groups of different reactivity, hydroxyl and other functional groups. Several procedures have been proposed for solving this problem. The determination of norepinephrine and dopamine in brain tissue was described by Maruyama and Takemori [90]. Dried residue from the extraction... 

Side effects are probabiy caused in part by actions of norepinephrine and dopamine in brain areas with undesired effects (e.g., insomnia, tremor, agitation, headache, dizziness)... 

Another biomedical example of modern voltammetry is a rapid scan cyclic voltammetric technique that has been used to quantify dopamine in brain tissue of freely moving animals. In this application, oxidation of dopamine to a quinone species at an implanted microcarbon electrode (at approximately -i0.600 V vs. Ag/AgCl) yields peak currents proportional to dopamine levels. The electrode can be used to measure this neurotransmitter in different regions of the brain or in a frxed location. Often, pharmacological or electrical stimulation can be employed to measure the... 

Bertler, a. and Rosengren, E., Occurrence and distribution of dopamine in brain and other tissues, Experientia 15, 10 (1959). 

Ptd-Ser is thought to play a key role for the activity of various membrane-bound enzymes. Recently, this lipid has been demonstrated to take part in the glucagon-responsiveness of adenylate cyclase in liver (Pohl et al., 1971) and heart (Levey, 1971), in the activation of tyrosine hydroxylase in rat brain striatal synapto-somes (Raese et al., 1976), in the increased turnover of dopamine in brain (Toffano Leon, this volume) and in other functional parameters. 

Sood P, Cole S, Fraier D, Young AM. Evaluation of metaquant microdialysis for measurement of absolute concentrations of amphetamine and dopamine in brain a viable method for assessing pharmacokinetic profile of drugs in the brain. J Neurosci Meth 2009 185 39-44. 

In the periphery, dopamine receptor levels are generally lower than those observed in brain, particularly in comparison to striatal dopamine receptor levels. Due to these low levels, knowledge of receptor distribution in the periphery is not yet comprehensive. Nevertheless, Dl-like receptors have been reported in the parathyroid gland and in the tubular cells of the kidney. D2-like dopamine receptors have also been observed in the kidney. In addition, dopamine D2 and D4 receptors have been found in the adrenal cortex, where they modulate aldosterone secretion. The... 

The nigrostriatal tract is one of the four main dopaminergic pathways in the central nervous system. About 75% of the dopamine in the brain occurs in the nigrostriatal pathway with its cell bodies in the substantia nigra, whose axons project in the corpus striatum. Degeneration of the dopaminergic neurons in the nigrostriatal system results in Parkinsons disease. 

The symptoms of parkinsonism are caused by a depletion of dopamine in the CNS. Dopamine, when given orally, does not cross the blood-brain barrier and therefore is ineffective The body s blood-brain barrier is a mesh-work of tightly packed cells in die walls of the brain s capillaries that screen out certain substances. This unique meshwork of cells in the CNS prohibits large and potentially harmful molecules from crossing into die brain. This ability to screen out certain substances lias important implications for drug dierapy because some drugs are able to pass through die blood-brain barrier more easily dian odiers. 

The exact mechanism of action of these dm is not understood. It is thought that these drug s act directly on postsynaptic dopamine receptors of nerve cells in the brain, mimicking die effects of dopamine in the brain. 

CBs, like OPs, can cause a variety of sublethal neurotoxic and behavioral effects. In one study with goldfish Carrasius auratus), Bretaud et al. (2002) showed effects of carbofuran on behavioral end points after prolonged exposure to 5 pg/L of the insecticide. At higher levels of exposure (50 or 500 pg/L), biochemical effects were also recorded, including increases in the levels of norepinephrine and dopamine in the brain. The behavioral endpoints related to both swimming pattern and social interactions. Effects of CBs on the behavior of fish will be discussed further in Chapter 16, Section 16.6.1. 

It is generally felt that a substance is more likely to be a NT if it is unevenly distributed in the CNS although if it is widely used it will be widely distributed. Certainly the high concentration (5-10 pmol/g) of dopamine, compared with that of any other monoamine in the striatum or with dopamine in other brain areas, was indicative of its subsequently established role as a NT in that part of the CNS. This does not mean it cannot have an important function in other areas such as the mesolimbic system and parts of the cerebral cortex where it is present in much lower concentrations. In fact the concentration of the monoamines outside the striatum is very much lower than that of the amino acids but since the amino acids may have important biochemical functions that necessitate their widespread distribution, the NT component of any given level of amino acid is difficult to establish. 

Kebabian, JW and Caine, DB (1979) Multiple receptors for dopamine. Nature 277 93-96. Kitai, ST, Sugimori, M and Kocsis, JC (1976) Excitatory nature of dopamine in the nigro-caudate pathway. Exp. Brain Res. 24 351-363. 

Ungerstadt, U and Arbuthnott, GW (1970) Quantitative recording of rotational behaviour in rats after 6-hydroxy dopamine lesions of the nigrostriatal dopamine system. Brain Res. 24 485-493. 

The localisation of a particular peptide to a particular brain area and possibly associated with a particular transmitter (e.g. CCK with dopamine in mesolimbic pathways) has often prompted a prediction of function (e.g. CCK may have a role in schizophrenia). Animal studies in which the peptide has been injected into the appropriate brain area or tested on slices taken from the brain area have sometimes been taken to confirm such hypotheses. These approaches have lined up the peptides for a whole range of potential roles, some of which are listed in Table 12.4. Whether these predictions are realities will depend on the availability of chemical agents and their evaluation, not only in animals but also in humans. 

COMMENT We feel that it is due to the formation of 5,6-DHT in the eortex. These cells are indeed innervated by serotonin cells and, as a matter of fact, we have an experiment that is being published in Brain Research where we show that if we injeet 5,6-DHT into the ventricles, we ean produce exactly the same type of degeneration in the pyramidal cells, due to the formation of the 5,6 from the 5-hydroxytryptamine. We are exploring the possibility of it being another catecholamine in addition to dopamine, so I think both of those may be helpful in answering your question. 

There are several ways in which possible neurotoxic effects might be studied. First, measurement of cerebrospinal fluid concentrations of dopamine or serotonin metabolites would be a straightforward way of assessing neurotoxicity. There are pitfalls in this approach (as outlined by Dr. Ricaurte (this volume), such as the facts that lumbar cerebrospinal fluid might reflect spinal cord neurochemistry more than it reflected brain neurochemistry, and drugs like /r-chloroamphetamine affect serotonin neurons in spinal cord less than they do those in brain (Sanders-Bush... 

A second approach might be to measure dopamine and serotonin along with their metabolites and other specific neuronal constituents such as tyrosine hydroxylase and tryptophan hydroxylase or uptake carrier sites in brain tissue obtained at autopsy. Accumulating data in this way might be a slow and tedious process, and drug dosing history might be uncertain and variable nonetheless, the approach deserves consideration. 

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