Dopamine levels

Genetic disruption of dopamine synthesis in mice lacking TH shows that dopamine is not essential for development. However, dopamine deficient mice do not survive long after weaning unless treated with l-DOPA. These mice display severe aphagia and adipsia and loss of motor function. While these mice have a major reduction in dopamine levels some residual dopamine can be detected that is generated through the action of tyrosinases. 

Cytotoxics cause an elevation of dopamine levels in the area postrema in animal studies and may release prostaglandins and inhibit enzymes such as enkepha-linases to allow increased levels of enkephalins to activate opioid receptors on dopaminergic nerves. 

Neurotransmitter Transporters. Figure 3 Dopamine turnover at a presynaptic nerve terminal, (a) Dopamine is produced by tyrosine hydroxylase (TH). When secretory vesicles are filled, they join the releasable pool of vesicles at the presynaptic membrane. Upon exocytosis, the diffusion of released dopamine is limited by reuptake via DAT. (b) If DAT is inactive, dopamine spreads in the cerebrospinal fluid but cannot accumulate in secretory vesicles. This results in a compensatory increase of dopamine hydroxylase activity and a higher extracellular dopamine level mice with inactive DAT are hyperactive. 

Psychostimulants. Figure 3 Effect of methylphenidate depending on baseline tonic (T) and phasic (P) dopamine levels. In a normal state only minimal changes are noted (which points to a rather low abuse potential). From a hypoactive state, methylphenidate increases both Tand P levels. However, this is much more true for the strongly lowered P tone. In contrast, in moderately hyperactive states and ADHD, T levels are increased and P levels are decreased, respectively, correlating with the baseline levels (adapted from [2]). 

Disulfiram produces a variety of adverse effects, which commonly include drowsiness, lethargy, and fatigue (Chick 1999). Other more serious adverse effects, such as optic neuritis, peripheral neuropathy, and hepatotoxicity, are rare. Psychiatric effects of disulfiram are also uncommon. They probably occur only at higher dosages of the drug and may result from the inhibition by disulfiram of a variety of enzymes in addition to ALDH. Included among the enzymes inhibited by disulfiram is dopamine P-hydroxylase, inhibition of which increases dopamine levels, which in turn can exacerbate psychotic symptoms in patients with schizophrenia and occasionally may result in psychotic or depressive symptoms in patients without schizophrenia. 

If you look at the court records, you see that story repeatedly, i.e., this reactive component. And you can see the same thing in chronic animals. You do have to take them out to a 3- or 6-month period to see those effects. During long-term chronic use, the dopamine at that point is markedly depleted. We are talking about animals that have 20 or 30 percent of the original dopamine levels a month or so after they have been given the last dose of amphetamine. 

Shafiq-ur-Rehman. 1991. Effects of lead on the behavioral complex stereotypes and regional brain dopamine levels in rats. Arch Environ Contain Toxicol 20 527-530. 

Insight into the state of dopaminergic tone is best obtained from measurements of extracellular dopamine in microdialysate samples collected from the behaving organism. Striatal (Paulson and Robinson 1994 Smith et al. 1992 Castaneda et al. 2004) and prefrontal cortical (Feenstra et al. 2000) dopamine levels rise in anticipation of, and are maintained throughout, the major wakefulness period in the rat, in concert with declines in dopamine metabolites (i.e., DOPAC, HVA, and 5-HIAA) (Smith et al. 1992 Whittaker et al. 1997). This pattern is... 

Sowers J. R., Vlachakis N. (1984). Circadian variation in plasma dopamine levels in man. J. Endocrinol. Invest. 7(4), 341-5. 

Pistis, M., Ferraro, L., Flore, G., Tanganelli, S., Gessa, G.L., and Devoto, P., Delta(9)-tetrahydrocan-nabinol decreases extracellular GABA and increases extracellular glutamate and dopamine levels in the prefrontal cortex an in vivo microdialysis study, Brain Res., 948, 155, 2002. 

Chen, J., Marmur, R., Pulles, A., Paredes, W., and Gardner, E.L., Ventral tegmental microinjection of A9-tetrahydrocannabinol enhances ventral tegmental somatodendritic dopamine levels but not forebrain dopamine levels evidence for local neural action by marijuana s psychoactive ingredient, Brain Res., 621, 65, 1993. 

Fornstedt, B., Carlsson, A. A marked rise in 5-S-cysteinyl-dopamine levels in guinea-pig striatum following reserpine treatment. J. Neural Transm. 76 155, 1989. 

Bowyer, J.F., Tank, A.W., Newport, G.D. et al. The influence of environmental temperature on the transient effects of methamphetamine on dopamine levels and dopamine release in rat striatum. J. Pharmacol. Exp. Ther. 260 817, 1992. 

Kankaanpaa, A., Meririnne, E., Lillsunde, P., and Seppala, T., The acute effects of amphetamine derivatives on extracellular serotonin and dopamine levels in rat nucleus accumbens, Pharmacol. Biochem. Behav. 59(4), 1003-1009, 1998. 

Inside the cytoplasm of the presynaptic neuron the monoamines are exposed to the mitochondrial outer membrane-bound enzyme monoamine oxidase (MAO). MAO breaks the monoamines down into inactive metabolites before they are taken up into the vesicles. However, if MAO is inhibited, then the monoamines enter the vesicles and are available for release. MAO inhibitors, such as moclobemide, have been used in the treatment of depression, since they increase the availability of noradrenaline and serotonin. Selegiline is used for Parkinson s disease, since it raises dopamine levels. 

Another crucial problem for any neurochemical model is cause and effect. Neuroleptics have a high affinity for dopamine receptors, particularly the D2-subtype. There is also a highly significant positive correlation (r > +0.9) between this receptor binding and their clinical potency (Seeman, 1980). But, this does not necessarily implicate elevated dopamine levels as the cause of schizophrenia. Moreover, blockade of dopamine receptors happens very rapidly, whereas clinical benefits are only seen after chronic treatment. Rose (1973) has criticised the reductionist statement that an abnormal biochemistry causes schizophrenia because it relates cause and effect at different organisational levels (namely, the molecular and behavioural). But, while it can be legitimate to discuss cause and effect at the same level that chlorpromazine blocks dopamine receptors (one molecule altering the response of another), it is not valid to infer that increased dopamine activity causes schizophrenia. Put another way ... 

Dyskinesias are involuntary choreiform movements, usually involving the neck, trunk, and extremities. They are usually associated with peak striatal dopamine levels. Less commonly, dyskinesias also can develop during the rise and fall of L-dopa effects (the dyskinesias-improvement-dyskinesias or diphasic pattern of response. 

Lazarini CA, Florio JC, Lemonica IP et al (2001) Effects of perinatal exposure to deltamethrin on forced swimming behavior, motor activity, and striatal dopamine levels in male and female rats. Neurotoxicol Teratol 23 665-673... 

Intracellular Fe is usually tightly regulated, being bound by ferritin in an insoluble ferrihydrite core, and impaired Fe homeostasis has been linked to Parkinson s disease and Alzheimer s disease. A consistent neurochemical abnormality in Parkinson s disease is degeneration of dopaminergic neurons relating to a reduction of striatal dopamine levels. As tyrosine hydroxylase (Fig. 24) (494), an Fe enzyme, catalyzes the formation of l-DOPA, the rate-limiting step in the biosynthesis of dopamine, the disease can be considered as a tyrosine... 

Mice exposed for 28 days to phenol in drinking water exhibited a significant reduction in dopamine level in the corpus striatum at the 1.8 mg/kg/day dose, and significantly decreased levels of norepinephrine, serotonin, and 5-hydroxyindoleacetic acid in the hypothalamus at the 6.2 mg/kg/day dose (Hsieh et al. 1992). Levels of neurotransmitters in other brain regions were also significantly altered at higher doses of phenol. 

Monoamine Arecoline has indirect effects on catecholamine levels (Molinengo et al. 1986). Significant reductions occur in norepinephrine levels, but increases occur in dopamine levels in both cortical and subcortical areas. 

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