Dopamine Turnover

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. 

Lemmer B., Berger T. (1978). Diurnal rhythm in the central dopamine turnover in the rat. Naunyn Schmiedebergs Arch. Pharmacol 303(3), 257-61. 

Dere, E., Souza-Silva, M. A., Topic, B., Spieler, R. E., Haas, H. L. and Huston, J. P. Histidine-decarboxylase knockout mice show deficient nonreinforced episodic object memory, improved negatively reinforced water-maze performance, and increased neo- and ventro-striatal dopamine turnover. Learn. Mem. 10 510-519, 2003. 

Indirect mechanisms Nicotine has indirect effects on monoamine systems. A considerable amount of research has examined the relationships between nicotine and dopamine activity in the brain, in light of dopamine s role in reinforcement and nicotine s addictive properties. Nicotine increases dopamine turnover in the striatum and cerebral cortex (Clarke and Reuben 1996 Tani et al. 1997 Nanri et al. 1998). It also increases burst activity in dopamine neurons of the ventral tegmental area (VTA), a primary source of dopamine to the forebrain (Nisell et al. 1995 Fisher et al. 1998). Such a firing pattern in the VTA is associated with processes of reinforcement, learning, and cognitive activity. Nicotine actions on dopaminergic neurons occur at both somatodendritic sites and synaptic terminals. Further, both systemic nicotine and direct administration into the VTA increase dopamine release in the nucleus ac-... 

Monoamines Ginseng has complex effects on endogenous monoamines. After two weeks of treatment, turnover of dopamine and norepinephrine is increased in the cerebral cortex, and serotonin turnover is increased in the striatum and cerebellum (Itoh et al. 1989). However, dopamine turnover in the striatum is reduced, as is serotonin in the hypothalamus and midbrain. After seven weeks of treatment, on the other hand, serotonin turnover in the cerebellum is increased, but turnover of dopamine, norepinephrine, and serotonin is reduced in all other areas studied. Ginsenosides Rbl and Rgl decrease 5-HT levels or reduce 5-HT turnover (Zhang et al. 1991). There is no specific binding observed of Rgl and Rbl adrenergic (ol o2, or j8), dopamine, or 5-HT receptors. 

Ethanol, nicotine, caffeine, and phencyclidine stimulate both locomotor activity and dopamine turnover (Wise 1987). Sex differences in DA outflow in the NAC has been shown in response to ethanol. Female rats have a greater ethanol-induced DA outflow, as measured by microdialysis in the NAC, than males and this sexually dimorphic response is regionally specific as it is not observed in the striatum additionally, females consume more alcohol (Blanchard et al. 1993). 

Both clinical and experimental studies have provided evidence that 5-HT can also regulate dopamine turnover. Thus several investigators have shown that a positive correlation exists in depressed patients between the homovaniUic acid (HVA), a major metabolite of dopamine, and 5-HIAA concentrations in the CSF. In experimental studies, stimulation of the 5-HT cell bodies in the median raphe causes reduced firing of the substantia nigra where dopamine is the main neurotransmitter. There is thus convincing evidence that 5-HT plays an important role in modulating dopaminergic... 

The mechanism of action of valproate is complex and still the subject of uncertainty. The drug appears to act by enhancing GABAergic function. Thus it increases GABA release, inhibits catabolism and increases the density of GABA-B receptors in the brain. There is also evidence that it increases the sensitivity of GABA receptors to the action of the inhibitory transmitter. Other actions that may contribute to its therapeutic effects include a decrease in dopamine turnover, a decrease in the activity of the NMDA-glutamate receptors and also a decrease in the concentration of... 

The anticonvulsant properties of the drug would appear to be due to its ability to inhibit fast sodium channels, which may be unrelated to its psychotropic effects. Like lithium, it has been shown to decrease the release of noradrenaline and reduce noradrenaline-induced adenylate cyclase activity unlike lithium, it seems to have little effect on tryptophan or 5-HT levels in patients at therapeutically relevant concentrations. It also reduces dopamine turnover in manic patients and increases acetylcholine... 

Davis M, Myers KM (2002) The role of glutamate and gamma-aminobutyric acid in fear extinction clinical implications for exposme therapy. Biol Psychiatry 52 998-1007 Davis M, Whalen PJ (2001) The amygdala vigilance and emotion. Mol Psychiatry 6 13-34 Davis M, Hitchcock JM, Bowers MB, Berridge CW, Meha KR, Roth RH (1994) Stress-induced activation of prefrontal cortex dopamine turnover blockade by lesions of the amygdala. Brain Res 664 207-210... 

The antischizophrenic actions of these drugs may not consist simply of postsynaptic blockade of hyperactive dopamine systems. Such a blockade occurs within hours, while most symptoms improve over weeks. This discrepancy in the latency to therapeutic effect has been hypothesized to be linked to drug-induced changes in dopaminergic activity after initiation of therapy, dopamine turnover increases, but after continued antipsychotic treatment, tolerance develops and dopamine metabolism returns to normal. This downward adjustment of dopaminergic activity is consistent with the decreased plasma concentrations of the dopamine metabolite homovanillic acid, an observation that correlates temporally with the clinical response to drug treatment. 

Male New Zealand White rabbits (2200 g) were exposed to 750 ppm [3.25 g/m ] ethylbenzene for 12 h per day for seven days. Twelve or 24 h following the final day of exposure, the rabbits were killed and their brains dissected. Ethylbenzene depleted both striatal and tubero-infundibular dopamine levels (Mutti et al, 1988). In male Sprague-Dawley rats exposed to 2000 ppm [8.70 g/m ] ethylbenzene for 6 h per day for three consecutive days and killed 16-18 h following the last exposure, ethylbenzene increased dopamine and noradrenaline levels and turnover in the hypothalamus and the median eminence. Ethylbenzene exposure also reduced the secretion of prolactin and increased dopamine turnover within the dopamine-cholecystokinin-8 immunoreactive nerve terminals of the nucleus accumbens (Andersson et al, 1981). 

Lee E. S. Y., Soliman K. F. A., and Charlton C. G. (2005c). Lysophosphatidylcholine decreases locomotor activities and dopamine turnover rate in rats. NeuroToxicology 26 27-38. 

Dopamine agonists decrease pituitary prolactin secretion through a dopamine-mimetic action on the pituitary at two central nervous system loci (1) they decrease dopamine turnover in the tuberoinfundibular neurons of the arcuate nucleus, generating increased hypothalamic dopamine and (2) they act directly on pituitary dopamine receptors to inhibit prolactin release. 

Sofar (presynaptic) dopamine receptors mediating inhibition of dopamine turnover and/or release seem to display features resembling those of the D-2 receptor. However inconsistencies reported could finally lead to a subdivision of D-2 receptors in the near future or it will appear that some in vitro experimental conditions have been too extreme, which by itself would have induced changes in the pharmacological characteristic of the receptor. One obvious question emerging from this review is whether all D-2 dopamine receptors in the neostriatum are linked to an adenylate cyclase. With the methodology presently available it will be hopefully only a matter of time to answer this question. 

The title compounds 163 (and their metabolites 164 and 165), needed for accurate determination of dopamine turnover rate using PET198,199, have been synthesized200 with [18F]F2201 (equation 99). The mixtures of 2- and 6-[18F]fluoro derivatives obtained have been separated by reverse-phase HPLC and identified by 19F NMR201. 

Murphy BL, Arnsten AF, Goldman-Rakic PS, Roth RH. 1996a. Increased dopamine turnover in the prefrontal cortex impairs spatial working memory performance in rats and monkeys. Proc Natl Acad Sci USA 93 1325-1329. 

Bowers MB Jr. 1974. Central dopamine turnover in schizophrenic syndromes. Arch Gen Psychiatry 31 50-54. 

Murotani T, Ishizuka T, Hattori S, Hashimoto R, Matsuzaki S, et al. 2007. High dopamine turnover in the brains of Sandy mice. Neurosci Lett 421 47-51. 

Moreover, animals forced to turn in circles by running on a circular treadmill, as opposed to those trained to turn laterally as a conditioned response, also show bilateral rather than unilateral elevations in dopamine turnover (Sabol et al., 1990). 

Analysis of the regional changes in dopamine turnover in rats trained to use just one forelimb for bar pressing indicates significant increases in dopamine turnover bilaterally, in particular in the posterior and the lateral areas of the striatum (Church et al., 1986). In like vein, Cousins and Salamone trained rats on a fixed ratio 5 (FR5) schedule of... 

The last decade has provided new molecular and genetic tools for the analysis of changes in the dopamine turnover, particularly in the generation of strains of knockout mice that are deficient in various aspects of dopamine neurone development, in the cellular machinery for dopamine neurotransmission, or in other genes associated with parkinsonism in man. As several good recent reviews are available (Jankowsky et al., 2002 Eells, 2003), the present account will focus on the behavioral phenotypes associated with genetic manipulation of dopamine systems of the forebrain. 

Goeders NE, Smith JE (1993) Intracranial cocaine self-administration into the medial prefrontal cortex increases dopamine turnover in the nucleus accumbens. J Pharmacol Exp Ther 265 592-600. 

Fuxe K, Hokfelt T, Nilsson O (1972) Effect of constant light and androgen-sterilization on the amine turnover of the tuberoinfundibular dopamine neurons blockade of cyclic activity and induction of a persistent high dopamine turnover in the median eminence. Acta Endocrinol <59 625-639. 

Lookingland KJ, Moore KE (1985) Differential effects of morphine on the rates of dopamine turnover in the neural and intermediate lobes of the rat pituitary gland. Life Sci 37 1225-1229. 

Selmanoff MK (1985) Rapid effects of hyperprolactinemia on basal prolactin secretion and dopamine turnover in the medial and lateral median eminence. Endocrinology 775 1943-1952. 

Selmanoff MK, Wise PM (1981) Decreased dopamine turnover in the median eminence in response to suckling in the lactating rat. Brain Res 272 101-115. 

Anden NE (1972) Dopamine turnover in the corpus striatum after treatment with neuroleptic and antiacetylcholine drugs. J Pharm Pharmacol 24 905-906. 

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