6-Hydroxydopamine hydrobromide (Synonyms: 6-hydroxy Dopamine, Oxidopamine, 2,4,5-Trihydroxyphenethylamine)

6-Hydroxydopamine hydrobromide (6-OHDA) is a structural analogue of catecholamines, dopamine and noradrenaline, and exerts its toxic effects on catecholaminergic neurons. The neurotoxin 6-hydroxydopamine continues to constitute a valuable topical tool used chiefly in modeling Parkinson's disease (PD) in the rat ^[1].

The classical method of intracerebral infusion of 6-Hydroxydopamine hydrobromide, involving a massive destruction of nigrostriatal dopaminergic neurons, is largely used to investigate motor and biochemical dysfunctions in Parkinson's disease ^[1]

6-Hydroxydopamine hydrobromide undergoes robust auto-oxidation generating cytotoxic H2O2, reactive oxygen species (ROS) and catecholamine quinones which attack endocellular nucleophilic groups ^[2].

Neurotoxic effects of 6-Hydroxydopamine hydrobromide occur through a two-step mechanism involving accumulation of the toxin into catecholaminergic neurons, followed by alteration of cellular homeostasis and neuronal damage. Intracellular storage of 6-Hydroxydopamine hydrobromide is mediated by the dopamine or noradrenaline membrane transporters (DAT and NAT respectively), which recognize and uptake 6-Hydroxydopamine hydrobromide due to its structural similarity with endogenous catecholamines ^[3]. 6-Hydroxydopamine hydrobromide is infused unilaterally in the MFB, producing a functional imbalance between the dopaminergic nigrostriatal systems and resulting in motor slowness, indicative of parkinsonian-like akinesia, and typical rotational behaviour in response to dopaminomimetic agents ^[4].

References:
[1]. Simola N, Morelli M, Carta A R. The 6-hydroxydopamine model of Parkinson's disease[J]. Neurotoxicity research, 2007, 11(3): 151-167.
[2]. Palumbo A, A Napolitano, P Barone and M d'Ischia (1999) Nitrite- and peroxide-dependent oxidation pathways of dopamine: 6-nitrodopamine and 6-hydroxydopamine formation as potential contributory mechanisms of oxidative stress- and nitric oxide-induced neurotoxicity in neuronal degeneration. Chem. Res. Toxicol. 12, 1213-1222.
[3]. Luthman J, A Fredriksson, E Sundstrom, G Jonsson and T.Archer (1989) Selective lesion of central dopamine or noradrenaline neuron systems in the neonatal rat: motor behavior and monoamine alterations at adult stage. Behav. Brain.Res. 33, 267-277.
[4]. Ungerstedt U and G Arbuthnott (1970) Quantitative recording of rotational behavior in rats after 6-hydroxydopamine lesions of the nigrostriatal dopamine system. Brain Res. 24, 485-493.