Substantia nigra lesions

Kang, U. J., Park, D. H Wessel, T Baker, H and Joh, T. H. (1992). DOPA-decar-boxylation in the striata of rats with unilateral substantia nigra lesions. Neurosci. Lett. 147 53-57. 

Pritzel M, Huston JP, Sarter M (1983) Behavioral and neuronal reorganization after unilateral substantia nigra lesions evidence for increased interhemispheric nigrostriatal projections. Neuroscience 9 879-888. 

Wachtel H, Kunow M, Loschmann PA (1992) NBQX (6-nitro-sulfamoyl-benzo-quinoxa-line-dione) and CPP (3-carboxy-piperazin-propyl phosphonic acid) potentiate dopamine agonist induced rotations in substantia nigra lesioned rats. Neurosci Lett 142 179-182... 

Trugman JM, Wooten GF (1987) Selective D1 and D2 dopamine agonists differentially alter basal ganglia glucose utilization in rats with unilateral 6-hydroxydopamine substantia nigra lesions. J. Neurosci, 7, 2927-2935. 

Sagar, S. M., and Snodgrass, S. R., 1980, Effects of substantia nigra lesions on forebrain 2-deoxyglucose retention in the rat. Brain Res. 185 335-348. 

A relationship between substantia nigra lesions, striatal DA and movement disturbance was demonstrated by making unilateral lesions in the ventromedial tegmentum of the upper brain stem. This caused loss of cells in the substantia nigra, decrease of striatal DA and NA but not 5HT and contralateral hypokinesis [130, 131]. If lesions were made in dorsomedial fibres of the cerebral peduncle then striatal 5HT decreased [132]. Lesions of the above types cause not only depletion of the amines but also of the enzymes necessary for their synthesis, tyrosine hydroxylase, tryptophan hydroxylase and aromatic amino acid decarboxylase [133, 134]. 

D2 Mostly in striatum, nucleus accumbens and olfactory tubercle but also on neuron cell bodies in substantia nigra and ventral tegmentum where they are the autoreceptors for locally (dendritic) released DA. The loss of specific D2 antagonist binding in the striatum after lesions of the afferent nigro-striatal tract indicates their presynaptic autoreceptor role on terminals there. Other lesion studies have also established D2 receptors on other inputs such as the cortico striatal tract. 

Control of motor function Nigrostriatal tract from substantia nigra (A9) Animals Stereotypy. Rotation if one tract is lesioned Humans Induces dyskinesias Effective in Parkinsonism Animals Catalepsy Humans Reduces dyskinesias Induces Parkinsonism Mainly D2 some Di ... 

People with Parkinson s disease show a specific degeneration of the nigrostriatal tract so DA must be linked in some way to the control of motor function. It is also known that an imbalance of DA function on the two sides of the rat brain, either by stimulation or lesion of one SN, causes off-line or rotational movement (Ungerstadt and Arbuthnott 1970). This is best shown some days after 6-OHDA lesion of one substantia nigra and its nigrostriatal pathway when systemic apomorphine (DA agonist) causes animals to turn away from the lesioned side (contraversive), presumably... 

Figure 7.7 Dopamine-induced rotation in the rat in which one (left) nigrostriatal dopamine pathway from the substantia nigra (SN) to the caudate putamen (CP) has been lesioned by a prior injection (14 days) of 6-hydroxydopamine. Amphetamine, an indirectly acting amine, releases DA and so can only act on the right side. Since the animal moves away from the dominating active side it induces ipsilateral rotation (i.e. towards the lesioned side). By contrast, the development of postS5maptic supersensitivity to DA on the lesioned side ensures that apomorphine, a directly acting agonist, is actually more active on that side and so the animal turns away from it (contralateral rotation)...

The injection of 6-OHDA into the rat nucleus accumbens produces the expected proliferation of DA receptors and resulting supersensitivity so that doses of apomorphine lower than normal produce a significant attenuation of PPI. This is not seen after the production of supersensitivity by toxin lesions of the substantia nigra and prefrontal cortex. The effects of amphetamine were also mainly modified by accumbens lesions. Thus as DA agonists primarily augment the positive symptoms such findings link these with the accumbens. 

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. 

The extent of receptor supersensitivity after unilateral nigrostriatal lesions can be quantified by measuring the extent of rotational behavior. After selective nigrostriatal lesions have been produced in rats by injections of 6-hydroxydopamine into the substantia nigra, the number of dopamine receptors in the ipsilateral corpus striatum increases markedly, and the increase in the number of receptors may correlate with the extent of behavioral supersensitivity as monitored by rotational behavior [52]. Thus, the increase in receptor density appears to play a role in the behavioral supersensitivity of these animals. 

Mavridis M, Degryse AD, Lategan AJ, Marien MR, Colpaert FC (1991) Effects of locus coeruleus lesions on parkinsonian signs, striatal dopamine and substantia nigra cell loss after l-methyl-4-phenyl-l,2,3,6-tetrahydropyridine in monkeys a possible role for the locus coeruleus in the progression of Parkinson s disease. Neuroscience 41 507-523. 

As indicated in Table I, I-III and their R and S optical antipodes were studied for dopaminergic activity in four primary tests (1) stimulation of central DA-sensitive adenylate cyclase (2, 35), (2) displacement of [%]-spiroperidol binding to rat caudate homogenate (35, 40), (3) induction of rotations in rats with unilateral lesions of the left substantia nigra (2, ... 

Morelli M, Carboni E, Devoto S, Di Chiara G (1987) 6-Hydroxydopamine lesions reduce specific [3H]sulpiride binding in the rat substantia nigra direct evidence for the existence of nigral D-2 autoreceptors. Eur J Pharmacol 740 99-104. 

Cole DG, Kobierski LA, Konradi C, Hyman SE (1994) 6-Hydroxydopamine lesions of rat substantia nigra up-regulate dopamine-induced phosphorylation of the cAMP-response element-binding protein in striatal neurons. Proc Natl Acad Sci USA 97 9631-9635. 

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