YOU ARE NOW CONNECTED TO THE TOXLINE (1981 FORWARD, NON-ROYALTY) FILE. ==PARKINSON'S AND 6-OHDA - RAT== 10 AUTHOR Zigmond MJ AUTHOR Berger TW AUTHOR Grace AA AUTHOR Stricker EM TITLE Compensatory responses to nigrostriatal bundle injury. Studies with 6-hydroxydopamine in an animal model of parkinsonism. SOURCE Mol Chem Neuropathol; VOL 10, ISS 3, 1989, P185-200 (REF: 65) ABSTRACT Intracerebral injections of the neurotoxin 6-hydroxydopamine (6-HDA) can produce selective, near-total destruction of the dopamine (DA)-containing neurons of the nigrostriatal bundle. The dysfunctions in animals with these lesions show many parallels with those present in Parkinsonian patients. Among these are the extensive loss of DA neurons in the basal ganglia, neurological impairments including akinesia, paradoxical kinesia in response to activating conditions, and improved sensory-motor function after the administration of DOPA. Moreover, as with patients with preclinical Parkinsonism, 6-HDA-treated rats with less extensive lesions show few or no behavioral dysfunctions, but are unusually sensitive to the akinesia-inducing effects of stress and dopaminergic antagonists. In this review, we summarize the behavioral effects of 6-HDA-induced depletion of striatal DA in the rat and then focus on the compensatory changes that may underlie the preclinical stage of the disorder. These compensations appear to include an increase in the number of active DA neurons, an increase in the release of DA per impulse from residual terminals, and a decrease in the amount of DA inactivated by high affinity uptake. Collectively, these alterations permit a few residual DA neurons to maintain a normal level of control over cellular activity in the striatum. 1 AUTHOR He Y AUTHOR Thong PS AUTHOR Lee T AUTHOR Leong SK AUTHOR Shi CY AUTHOR Wong PT AUTHOR Yuan SY AUTHOR Watt F TITLE Increased iron in the substantia nigra of 6-OHDA induced parkinsonian rats: a nuclear microscopy study. SOURCE Brain Res; VOL 735, ISS 1, 1996, P149-53 ABSTRACT The trace elemental concentrations, including iron, in the substantia nigra (SN) of a 6-OHDA induced rat model of Parkinson's disease were measured using nuclear microscopy. Only rats that exhibited amphetamine induced rotation of more than 7 turns/min were used. The results showed that the iron levels were significantly increased in the 6-OHDA lesioned SN, compared with the intact contralateral SN, and the SN of normal control rats injected with ascorbic acid, which showed no significant difference in iron levels between injected and non-injected sides. In both 6-OHDA lesioned and ascorbic acid injected SN, there were no alterations in the levels of calcium, magnesium, copper and zinc. In the 6-OHDA lesioned SN there was an almost complete loss of tyrosine hydroxylase positive cells in the SN. These results suggested that the 6-OHDA induced dopaminergic cell death may be related to the increased iron. 3 AUTHOR Borlongan CV AUTHOR Sanberg PR TITLE Elevated body swing test: a new behavioral parameter for rats with 6-hydroxydopamine-induced hemiparkinsonism. SOURCE J Neurosci; VOL 15, ISS 7 Pt 2, 1995, P5372-8 ABSTRACT Parkinson's disease is characterized by a depletion of dopamine (DA) neurons in the nigrostriatal pathway. Stereotaxic injections of 6-hydroxydopamine (6-OHDA), a selective neurotoxin, into either the medial forebrain bundle or the substantia nigra result in a massive DA denervation of the nigrostriatal pathway. Following unilateral nigrostriatal DA depletion, hemiparkinsonian animals develop a stereotypical rotational behavior when challenged with DA agonists such as apomorphine. The drug-induced rotational behavior has been widely used as the behavioral index of hemiparkinsonian animals, but it has some limitations. Although asymmetries in the rotational behavior may indicate an imbalance of DA contents and release capacity in the bilateral nigrostriatal pathway, the behavior is a pharmacological reaction. Accordingly, the drug-induced rotation test is subject to sensitization effects. The present study proposes the elevated body swing test (EBST) as a measure of asymmetrical motor behavior of hemiparkinsonian animals in a drug-free state. The EBST simply involves elevating the animal by handling its tail and recording the frequency and direction of the swing behavior. Unilateral nigral 6-OHDA-lesioned rats exhibited significant biased swing activity with the direction contralateral to the lesioned side, corresponding to the direction of apomorphine-induced rotations. A 30 sec EBST was noted as the peak time for biased swing activity. At 7 d postlesion (the start of testing), and every week thereafter for a period of 2 months, a fairly stable biased swing activity level was observed. At 1 and 2 months postlesion, the same animals were also challenged with apomorphine. (ABSTRACT TRUNCATED AT 250 WORDS) 5 AUTHOR Jolicoeur FB AUTHOR Rivest R AUTHOR St-Pierre S AUTHOR Drumheller A TITLE Antiparkinson-like effects of neurotensin in 6-hydroxydopamine lesioned rats. SOURCE Brain Res; VOL 538, ISS 2, 1991, P187-92 ABSTRACT The aim of the present study was to examine the effects of neurotensin in an animal model of Parkinson's disease (PD). Bilateral administration of 6-OHDA in the medial forebrain bundle at the level of the posterolateral hypothalamus of rats resulted in the appearance of the 3 principal neurological signs of PD: hypokinesia, rigidity and tremor. These symptoms were accompanied by severe losses of dopamine and its main metabolites in terminal regions of well-known dopamine pathways. Norepinephrine concentrations were also decreased in several regions but to a lesser extent than dopamine. Intracerebroventricular administration of neurotensin, in doses ranging from 7.5 to 120.0 micrograms, resulted in dose related attenuations of both muscular rigidity and tremors of animals. However, hypokinesia, defined as decreased motor activity was not significantly affected by the peptide. Administration of 120.0 micrograms of [Ala]NT, an inactive analogue of neurotensin, failed to alter any of the 3 neurological signs. Together, these results reveal selective antiparkinson-like effects of neurotensin in an animal model. The theoretical significance of these findings is discussed.