Dopamine depletion

COMMENT The main point that 1 wanted to make is that it is very important to attempt to develop models where one is looking at least at some sort of in vivo integrated preparation. We look at serotonin depletion. We look at dopamine depletion. We have a variety of different mechanisms. Again we really do not know what, at this point in time, the serotonin depletion is doing. I think 1 know what it means if you deplete dopamine beyond a certain level. But even there, it is difficult to put an exact degree of impairment on the levels of dopamine depletion that we see in most of these models. 

Ricaurte, G.A. Guillery, R.W. Seiden, L.S. and Schuster, C.R. Nerve terminal generation after a single injection of [Pg.355]

Leng A., Mura A., Hengerer B., Feldon J., Ferger B. (2004). Effects of blocking the dopamine biosynthesis and of neurotoxic dopamine depletion with l-methyl-4-phenyl-l,2,3,6-tetrahydropyridine (MPTP) on voluntary wheel running in mice. Ilehav. Brain Res. 154, 375-83. 

Wagner, G.C., Carelli, R.M., Jarvis, M.F. Ascorbic acid reduces the dopamine depletion induced by methamphetamine and the 1-methy 1-4-phenyl pyridinium ion. Neuropharmacology. 25 559, 1986. 

Huang, N.K., Wan, F.J., Tseng, C.J., Tung, C.S. Nicotinamide attenuates methamphetamine-induced striatal dopamine depletion in rats. Neuroreport. 8 1883, 1997. 

Symptomatic treatment. The chorea of Huntington s disease responds (partially) to treatment with neuroleptics, which, through blockade of D2 receptors, may help to increase basal ganglia output to more normal levels. Dopamine-depleting agents, such as reserpine or tetra-benazine have also been used. At best, these agents are only moderately effective and they should only be used if the chorea truly interferes with activities of daily living or produces social embarrassment. Neuroleptics and... 

Dopamine depleting agents. Reserpine, a natural alkaloid that blocks vesicular transport of monoamines, depletes stored monoamines, including DA. DA depletion is associated with the emergence of parkinsonism. This effect of reserpine was among the first clues that PD is the result of DA deficiency (see above). Generally, the parkinsonism resulting from reserpine is reversible. 

A recent study further supported the involvement of dopamine in the mechanism of antidepressants [82]. In this study, the antidepressant-like effect of citalo-pram, paroxetine, desipramine and imipramine in the mouse forced swim test (FST) was compared with and without dopamine depletion. It was found that lesioning with 6-OHDA did not affect the response of mice to desipramine and imipramine, whereas dopamine depletion abolished the antidepressant-like effect of citalopram and paroxetine. These results suggest that the antidepressant-like effect of SSRIs in the FST requires the activation of dopaminergic pathways. 

Gerrits MA, Van Ree JM (1996) Effect of nucleus accumbens dopamine depletion on motivational aspects involved in initiation of cocaine and heroin self-administration in rats. Brain Res 713 114-124... 

The most troublesome untoward effects of treatment with reserpine involve the CNS. Sedation and depression are the most common, although nightmares and thoughts of suicide also occur. Reserpine treatment, therefore, is contraindicated in patients with a history of severe depression. The occasional report of re-serpine-induced extrapyramidal symptoms, which are similar to those seen in patients with Parkinson s disease, is believed to be a result of dopamine depletion from neurons in the CNS. 

Moochhala. 1 Methyl 4 phenyh 1,2,3, 6 tetrahydropyridine induced neuro-toxicity partial protection against striato-nigral dopamine depletion in C57BL/6J mice by cigarette smoke ex-posure and by beta-naphthoflavone-pretreatment. Neurosci Lett 1991 127(2) 247-250. 

Brain morphometric studies of cocaine abusers have revealed evidence for enlargement of caudate and puta-men during initial abstinence, but no evidence for changes in total brain volume or volume of medial temporal lobe structures (Jacobsen et ah, 2001 a,b). Enlargement of basal ganglia structures likely reflects dopamine depletion that appears to develop following cessation of chronic cocaine use. 

In summary, treatments for tardive dyskinesia include cessation of the neuroleptic switching to a novel agent cholinergic agents and dopamine depleting drugs, such as reserpine or tetrabenazine. 

An increased incidence of depression in Parkinson s disease, as well as in patients receiving dopamine-depleting or antagonistic agents... 

High doses of reserpine characteristically produce sedation, lassitude, nightmares, and severe mental depression occasionally, these occur even in patients receiving low doses (0.25 mg/d). Much less frequently, ordinary low doses of reserpine produce extrapyramidal effects resembling Parkinson s disease, probably as a result of dopamine depletion in the corpus striatum. Although these central effects are uncommon, it should be stressed that they may occur at any time, even after months of uneventful treatment. Patients with a history of mental depression should not receive reserpine, and the drug should be stopped if depression appears. 

MPTP is a protoxin that is converted by monoamine oxidase to /V-methyl-4-phenylpyridinium (MPP+). MPP+ is selectively taken up by cells in the substantia nigra through an active mechanism normally responsible for dopamine reuptake. MPP+ inhibits mitochondrial complex I, thereby inhibiting oxidative phosphorylation. The interaction of MPP+ with complex I probably leads to cell death and thus to striatal dopamine depletion and parkinsonism. 

Dackis, Charles A., and Mark S. Gold. 1985. "New Concepts in Cocaine Addiction The Dopamine Depletion Hypothesis." Neuroscience and Biobehavioral Reviews 9 469-77. 

Fray, Paul J., Stephen B. Dunnett, Susan D. Iversen, Anders Bjorklund and Ulf Stenevi. 1983. "Nigral Transplants Reinnervating the Dopamine-Depleted Neostriatum Can Sustain Intracranial Self-Stimulation." Science 219 416-19. 

Elzaouk L, Leimbacher W, Turri M, Ledermann B, Biirki K, Blau N, Thony (2003) Dwarfism and low IGF-1 due to dopamine depletion in Pts—/— mice rescued by feeding neurotransmitter precursors and H4-biopterin. J Biol Chem 278 28303-28311... 

Gerfen CR. D1 dopamine receptor supersensitivity in the dopamine depleted striatum animal model of Parkinson s disease. Neuroscientist. 2003 9 455-462. 

Muscle-derived differentiation factor (MDF) induces tyrosine hydroxylase expression in a variety of central nervous system neurons, including those of striatum, cerebellum, and cortex. Normally, i.e., without MDF, these neurons do not express this enzyme of catecholamine synthesis. Further in vitro studies revealed that MDF enhances TH-mRNA 40-fold in fetal mesencephalic neurons. In vivo studies, employing infusion of partially isolated MDF, reported this molecule to enhance tyrosine hydroxylase activity in dopamine-depleted striata of 6-OHDA-lesioned animals. Furthermore, an increase of striatal dopamine concentrations and a partial compensation of rotational asymmetry were observed. In contrast, dopaminergic parameters were not affected by administration of MDF in control animals, suggesting that adult dopaminergic neurons may regain sensitivity toward differentiation factors after lesion. 

Aubin, N. et al., Aspirin and salicylate protect against MPTP-induced dopamine depletion in mice, J. Neuro-chem., 71, 1635-1642, 1998. 

Riekkinen M, Kejonen K, Jakala P, Soininen H, Riekkinen P, Jr. (1998) Reduction of noradrenaline impairs attention and dopamine depletion slows responses in Parkinson s disease. Eur. J. Neurosci. 10 1429-1435. 

The few studies that have tested for longer-term dopamine depletion from methylphenidate have failed to document it (Wagner et al., 1980 Yuan et al., 1997 Zaczek et al., 1989). However, this does not rule out irreversible neurotoxicity. Given the findings of short-term abnormalities, and the lessons from amphetamine and methamphetamine, suspicion must remain high that irreversible changes are also caused by methylphenidate. 

Ricaurte, G. A., Fuller, R. W., Perry, K. W., Seiden, L. S. (1983). Fluoxetine increases long-lasting neostriatal dopamine depletion after administration of d-methamphet-amine and d-amphetamine. Neuropharmacology, 22, 1165—1169. 

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