Dopamine brain concentrations

D. R. Cooper, C. Marrel, H. van de Waterbeemd, B. Testa, P. Jenner, C. D. Marsden, l-Dopa Esters as Potential Prodrugs Behavioural Activity in Experimental Models of Parkinson s Disease , J. Pharm. Pharmacol. 1987, 39, 627 - 635 D. R. Cooper, C. Marrel, H. van de Waterbeemd, B. Testa, P. Jenner, C. D. Marsden, L-Dopa Esters as Potential Prodrugs Effect on Brain Concentration of Dopamine Metabolites in Reserpi-nized Mice , J. Pharm. Pharmacol. 1987, 39, 809-818. 

In addition to behavior changes, exposure to the alarm odor also has physiological effects. For instance, in pearl dace, Semotilus margarita, the levels of plasma cortisol and glucose increase 15 minutes after the alarm and are back to normal after 5 hours. The brain concentrations of dopamine, norepinephrine, 5-hydroxytryptamine, or tryptophan did not change (Rehnberg et al., 1987). The fish recovered physiologically much sooner than the behavioral activation For example. Von Frisch (1941) observed that minnows avoided the site of their encounter with alarm substance for many hours, even days. 

An imprinted poly[tetra(o-aminophenyl)porphyrin] film, deposited on a carbon fibre microelectrode by electropolymerization, was used for selective determination of dopamine [208] in the potential range of —0.15 to 1.0 V. This chemosensor has been used successfully for dopamine determination in brain tissue samples. The dopamine linear concentration range extended from 10 6 to 10-4 M with LOD of 0.3 pM. However, this LOD value is very high compared to that of the dopamine voltammetric detection using polyaminophenol MIPs prepared by electropolymerization [209]. Dopamine was determined by CV and DPV at concentrations ranging from 2 x 10 s to 0.25 x 10 6 M with LOD of 1.98 nM. This LOD value is lower than that of PM dopamine detection [133]. 

The role that dopamine plays in regulating mood and emotional stability can be at least partially grasped by examining dopamine s role in schizophrenia and drug addiction. Schizophrenia is a disorder characterized by delusions, hallucinations, withdrawal from external reality, and emotional unresponsiveness. The dopamine theory of schizophrenia, proposed in 1965, attributes the disorder to elevated brain concentrations of dopamine or to a hypersensitivity of dopaminergic receptors, especially the D2 and D4 receptor subtypes. Several drugs used to treat schizophrenic patients bind to D2 and D4 receptors and block the dopaminergic response. 

Wightman RM, Zimmerman JB (1990) Control of dopamine extracellular concentration in rat striatum by impulse flow and uptake. Brain Res Rev 75 135-144. 

As in AD, knowdedge of the neurotransmitter deficiency underlying PD, in this case dopamine, has been the basis for the development of therapy. Early studies show ed that cerebral dopamine was concentrated in the shiatum and that levodopa, the precursor to dopamine, could reverse the akinetic effects of the dopamine-depleting agent reserpine in experimental animals (Carlsson et al., 1957, 1958). Eventually, the identification of shiatal dopamine depletion as a key neurochemical finding in parkinsonian brains lead to heatment wdth levodopa in humans and to the subsequent advent of compounds that mimic the effects of dopamine or prolong its action (Table 39.2). 

Modafinil is a wake-promoting agent whose specific biochemical mechanism of action is obscure. It increases brain concentrations of dopamine after chronic administration in animals but has no overtly stimulant effect like amphetamines. It appears to have a slow onset and its action lasts 8-12 h abuse potential is very low. Modafinil is used in narcolepsy and other hypersomnias and has also been studied in normal people who need to stay awake for long periods and fimction well. 

By increasing dopamine and y-aminobutyric acid, and influencing brain concentrations of serotonin, theanine can also help inhibit the stimulating effects of caffeine. - Theanine creates a sense of relaxation approximately 30-40 min after ingestion via at least two different mechanisms. First, this amino acid directly stimulates the production of a-brain waves, creating a state of deep relaxation and mental alertness similar to that achieved through meditation. Second, theanine is involved in the formation of the inhibitory neurotransmitter, y-aminobutyric acid, which influences the levels of two other neurotransmitters, dopamine and serotonin, producing the key relaxation effect. ... 

Swanson J. M. and Volkow N. D. 2003. Serum and brain concentrations of methylphenidate Implications for use and abuse. Neurosci. Biobehav. Rev. 27 615-621 Tabet F., Savoia C., Schiffrin E. L. and Touyz R. M. 2004. Differential calcium regulation by hydrogen peroxide and superoxide in vascular smooth muscle cells from spontaneously hypertensive rats. J. Cardiovasc. Pharmacol. 44 200-208 Tanda G., Pontieri F. E., Frau R. and Di C. G. 1997. Contribution of blockade of the noradrenaline carrier to the increase of extracellular dopamine in the rat prefrontal cortex by amphetamine and cocaine. Fur. J. Neurosci. 9 2077-2085... 

Variations on the dopamine hypothesis have also been proposed. Krause et al. (1985) reported a correlation between increased reaction time and decreased urinary dopamine in patients with PKU. As brain dopamine is concentrated in the corpus striatum, and the choice reaction time test requires a motor response as well as integration of stimuli, they speculate that the nigrocostriatal pathways are affected. Faust (1986-1987) obtained similar results they suspect that the deficits are associated with complex areas of the brain, such as the anterior frontal regions, and in motor areas that represent less advanced functions. 

Bonilla, E. and Diez-Ewald, M. (1974) Effects of L-dopa on brain concentrations of dopamine and homovanillic acid in rats after chronic manganese chloride administration, J. Neurochem. 22, 297-299. 

Fuxe K, Andersson K, Nilsen OG, et al Toluene and telencephalic dopamine selective reduction of amine mrnover in discrete DA nerve terminal systems of the anterior caudate nucleus by low concentrations of toluene. Toxicol Lett 12 115—123,1982 Cause EM, Mendez V, Geller I Exploratory smdies of a rodent model for inhalant abuse. Neurobehav Toxicol Teratol 7 143—148, 1985 Gentry JR, Hill C, Malcolm R New anticonvulsants a review of applications for the management of substance abuse disorders. Ann Clin Psychiatry 14 233—245, 2002 Gerasimov MR, Ferrieri RA, Schiffer WK, et al Smdy of brain uptake and biodistribution of [llCjtoluene in non-human primates and mice. Life Sci 70 2811 — 2828, 2002... 

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