The Unilateral 6-hydroxydopamine Lesion Model in Behavioral Brain Research. Analysis of Functional Deficits, Recovery and Treatments

Lesions with the neurotoxin 6-hydroxydopamine (6-OHDA) have provided an important tool to study dopamine neurons in the brain. The most common version of such lesions is the unilateral one where the toxin is placed in the area of mesencephalic dopamine cell bodies or their ascending fibers. This approach leads to a lateralized destruction of mesencephalic dopamine neurons and to a lateralized loss of striatal dopamine innervation. Such lesions have contributed substantially to neuroscientific knowledge both, at the basic and clinical level. Physiologically, they have been used to clarify the neuroanatomy, neurochemistry, and electrophysiology of mesencephalic DA neurons and their relationships with the basal ganglia; the relevant findings have been summarized in a previous review (Schwarting, R.K.W. and Huston, J.P. (1996) Unilateral 6-hydroxydopamine lesions of meso-striatal dopamine neurons and their physiological sequelae, Progress in Neurobiology 49, 215-266). Furthermore, 6-OHDA lesions have been used extensively to investigate the role of these dopamine neurons with respect to behavior, to examine the brain's capacity to recover from or compensate for specific neurochemical depletions, and to investigate the promotive effects of experimental and clinical approaches which are relevant for the treatment of Parkinson's disease. These findings are summarized here, including the spectrum of behavioral deficits (turning, sensory neglect, etc.), functional recovery and its possible mechanisms, the behavioral effects of widely used pharmacological challenges (amphetamines, apomorphine, selective receptor agonists, L-DOPA), and the effects of treatments which can promote recovery (like neuropeptides, neurotrophins, and grafts).