Dopamine 6-hydroxy

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. 

Deminiere, J.M. Simon, H. Herman, J.P. and Le Moal, M. 6-Hydroxy-dopamine lesion of the dopamine mesocorticolimbic cell bodies increases (-l-)-amphetamine self-administration. Psychopharmacology 83 281-284, 1984. 

Maker, H.S. Weiss, C. and Brannan. Amine-mediated toxicity The effects of dopamine, norepinephrine, 5-hydroxytryptamine, 6-hydroxy-dopamine, ascorbate, glutathione and peroxide on the in vitro activities of creatine and adenylate kinases in the brain of the rat. 

Rollema, J. De Vries, J.B. Westerink, B.H.C. Van Putten, F.M.S. and Horn, A.S. Failure to detect 6-hydroxy dopamine in rat striatum after the dopamine releasing drugs dexamphetamine, methylamphetamine and MPTP. Eur J Pharmacol 132 65-69, 1986. 

Fessler, R.G. Sturgeon, R. and Meltzer, H.Y. Phencyclidine-induced iosilateral rotation in rats with unilateral 6-hydroxy-dopamine-induced lesions of the substantia nigra. I ife Sci 24 1281-1288, 1979. 

Hydroxy dopamine is a selectively neuro toxic compound, which damages the sympathetic nerve endings. It can be seen from Figure 7.43 that 6-hydroxydopamine is structurally very similar to dopamine and noradrenaline, and because of this similarity it is actively taken up into the synaptic system along with other catecholamines. Once localized in the synapse, the 6-hydroxydopamine destroys the nerve terminal. A single small dose of 6-hydroxydopamine destroys all the nerve terminals and possibly the nerve cells as well. 

Srinivasan J, Schmidt WJ (2004b) Treatment with alpha2-adrenoceptor antagonist, 2-methoxy idazoxan, protects 6-hydroxy dopamine-induced Parkinsonian symptoms in rats neurochemical and behavioral evidence. Behav. Brain Res. 154 353-363. 

A much easier nitration reaction is that of catechol derivatives. It has been shown that HRP and LPO (and likely every peroxidase) nitrate dopamine to 6-nitrodopa-mine with the concomitant formation of low amounts of 6-hydroxy dopamine [110] (Fig. 6.9d). 

Ungerstedt U (1968) 6-Hydroxy-dopamine induced degeneration of central monoamine neurons. Eur J Pharmacol 5 107-110. 

Historically, varicosities have been thought to be the site of synaptic contact of dopamine axons in the striatum. The points of actual synaptic contact are so small that they are difficult to detect in a single thin electron microscopy (EM) sections serial sections are needed and synaptic specializations may only be present in one section. Studies using the serial EM have revealed that varicosities are not preferentially involved in synaptic contacts (Pickel et al., 1982 Freund et al., 1984 Groves et al., 1994). Counts of varicosities, therefore, do not necessarily reflect the dopamine synapse numbers it is necessary to use dopamine specific labels, such as antibodies to tyrosine hydroxylase (TH) or transporter-specific markers, such as 5-hydroxy-dopamine (5-OHDA) together with serial EM. 

Price MT, Fibiger HC (1975) Discriminated escape learning and response to electric shock after 6-hydroxy-dopamine lesions of the nigro-neostriatal dopaminergic projection. Pharmacol Biochem Behav 5 285-290. 

Parkinson s disease Oxidation of 6-hydroxy dopamine Decrease in glutatione pool (both GSH and GSSG)... 

Like DOPA and methyldopa, 6-hydroxydopa (Figure 10.20a) finds its way into catecholaminergic nerve terminals it is decarboxylated inside the cell to 6-hydroxy-dopamine. The latter compound, however, does not act as a false transmitter. Instead, it acts as an inhibitor of the mitochondrial respiratory chain, apparently by binding to com-... 

Vu TQ, Ling ZD, Ma SY, Robie HC, Tong CW, Chen EY, Lipton JW, Caivey PM (2000) Pramipexole attenuates die dopaminergic cell loss induced by inti aventi iculai 6-hydroxy dopamine. J Neui al Transm 107 159-176. 

Marek, G.J. Vosmer, G. and Seiden, L.S. The effects of monoamine uptake inhibitors and methamphetamine on neostriatal 6-hydroxy-dopamine (6-OHDA) formation, short-term monoamine depletions and locomotor activity in the rat. Brain Res 516 1-7, 19906. 

In reserpine- or 6-hydroxy-dopamine-treated rats (two models of Parkinson s disease) at the level of the basal ganglia (Di Marzo et al. 2000b Maccarrone et al. 2003c)... 

The mechanism of the destruction of the nerve terminals is thought to involve oxidation of 6-hydroxy dopamine to a //-quin one, the production of a free radical or of superoxide anion. It seems that a reactive intermediate is produced which reacts covalently with the nerve terminal and permanently inactivates it. 

Figure 16.7-15. Topaquinone and 6-hydroxy-dopamine as prosthetic groups of diamine oxidases.

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