Central European Journal of Biology

Effects of right-unilateral 6-hydroxydopamine infusion-induced memory impairment and oxidative stress: relevance for Parkinson's disease Abstract: Male Wistar rats were subjected to right-unilateral 6-hydroxydopamine (6-OHDA) (2 µg/µl) lesions of the ventral tegmental area (VTA) or the substantia nigra (SN), or were sham-operated, and their ability to acquire the operant task was studied by means of Y-maze and shuttle-box tasks. Lesions of both the VTA and the SN resulted in an impairment of conditioned avoidance response and increase of crossing latency tested by means of shuttle-box task, suggesting significant effects of long-term memory. 6-OHDA significantly decreased spontaneous alternation in Y-maze task, suggesting effects on spatial memory, especially on short-term memory. In addition, 6-OHDA lesions of the VTA and the SN induced reductions in superoxide dismutase (SOD), glutathione peroxidase (GPX) activities and malondialdehyde (MDA) levels in the temporal lobe rather than in the frontal lobe homogenates. Our results provide further support for the toxic effects of 6-OHDA-induced memory impairment and oxidative stress with relevance for Parkinson's disease.

[1]  S. Przedborski,et al.  Oxidative Stress in Parkinson's Disease , 2008, Annals of the New York Academy of Sciences.

[2]  K. Mohanakumar,et al.  Unilateral implantation of dopamine-loaded biodegradable hydrogel in the striatum attenuates motor abnormalities in the 6-hydroxydopamine model of hemi-parkinsonism , 2007, Behavioural Brain Research.

[3]  Y. Temel,et al.  High frequency stimulation of the subthalamic nucleus improves speed of locomotion but impairs forelimb movement in Parkinsonian rats , 2007, Neuroscience.

[4]  T. Nabeshima,et al.  Brain serotonin depletion impairs short-term memory, but not long-term memory in rats , 2007, Physiology & Behavior.

[5]  N. Morioka,et al.  Assessing an eating disorder induced by 6-OHDA and the possibility of nerve regeneration therapy by transplantation of neural progenitor cells in rats. , 2007, Nihon shinkei seishin yakurigaku zasshi = Japanese journal of psychopharmacology.

[6]  J. Deniau,et al.  Impact of 6‐hydroxydopamine lesions and cocaine exposure on µ‐opioid receptor expression and regulation of cholinergic transmission in the limbic–prefrontal territory of the rat dorsal striatum , 2007, The European journal of neuroscience.

[7]  E. Niki,et al.  Molecular mechanisms of 6-hydroxydopamine-induced cytotoxicity in PC12 cells: involvement of hydrogen peroxide-dependent and -independent action. , 2007, Free radical biology & medicine.

[8]  E. Dowd,et al.  Further validation of the corridor task for assessing deficit and recovery in the hemi-Parkinsonian rat: Restoration of bilateral food retrieval by dopamine receptor agonism , 2006, Behavioural Brain Research.

[9]  A. R. Cools,et al.  Bilateral nigral 6-hydroxydopamine lesions increase the amount of extracellular dopamine in the nucleus accumbens , 2005, Experimental Neurology.

[10]  Kiyofumi Yamada,et al.  Role of the mesotelencephalic dopamine system in learning and memory processes in the rat. , 2003, European journal of pharmacology.

[11]  Takashi Yamamoto,et al.  Ventral tegmental lesions reduce overconsumption of normally preferred taste fluid in rats , 2002, Behavioural Brain Research.

[12]  C. Thiel,et al.  Auditory noise can prevent increased extracellular acetylcholine levels in the hippocampus in response to aversive stimulation , 2000, Brain Research.

[13]  M. Georger,et al.  Disruption of acquisition and performance of operant response-duration differentiation by unilateral nigrostriatal lesions , 2000, Behavioural Brain Research.

[14]  C. Olanow,et al.  Oxidative stress and the pathogenesis of Parkinson's disease , 1996, Neurology.

[15]  T. Hasegawa,et al.  The role of nitric oxide in dizocilpine-induced impairment of spontaneous alternation behavior in mice. , 1996, The Journal of pharmacology and experimental therapeutics.

[16]  A. K. Agarwal,et al.  Free Radical‐Generated Neurotoxicity of 6‐Hydroxydopamine , 1995, Journal of neurochemistry.

[17]  J. Cadet,et al.  Vitamin E attenuates the toxic effects of 6-hydroxydopamine on free radical scavenging systems in rat brain , 1992, Brain Research Bulletin.

[18]  T. Kameyama,et al.  Denervation of dopaminergic neurons with 6-hydroxydopamine increases nerve growth factor content in rat brain , 1992, Neuroscience Letters.

[19]  Anthony G. Phillips,et al.  Dopamine functions in appetitive and defensive behaviours , 1992, Progress in Neurobiology.

[20]  J. Cooper,et al.  Irreversible Inhibition of Mitochondrial Complex I by 1‐Methyl‐4‐Phenylpyridinium: Evidence for Free Radical Involvement , 1992, Journal of neurochemistry.

[21]  R. Beninger,et al.  On the interpretation of asymmetries of posture and locomotion produced with dopamine agonists in animals with unilateral depletion of striatal dopamine , 1991, Progress in Neurobiology.

[22]  K. Takeshige,et al.  1-Methyl-4-phenylpyridinium (MPP+) induces NADH-dependent superoxide formation and enhances NADH-dependent lipid peroxidation in bovine heart submitochondrial particles. , 1990, Biochemical and biophysical research communications.

[23]  J N Sanes,et al.  Dopaminergic effects on simple and choice reaction time performance in Parkinson's disease , 1988, Neurology.

[24]  G. Koob,et al.  Neuroleptic-like distruption of the conditioned avoidance response requires destruction of both the mesolimbic and nigrostriatal dopamine systems , 1984, Brain Research.

[25]  B. J. Jones,et al.  THE EFFECTS OF INTRA‐AMYGDALOID INJECTIONS OF 6‐HYDROXYDOPAMINE ON AVOIDANCE RESPONDING IN RATS , 1976, British journal of pharmacology.

[26]  E. Tolosa,et al.  Cognitive dysfunction and dementia in Parkinson disease , 2007, Movement disorders : official journal of the Movement Disorder Society.

[27]  Patrik Brundin,et al.  Pathogenesis of Parkinson's disease: dopamine, vesicles and alpha-synuclein. , 2002, Nature reviews. Neuroscience.

[28]  M. Youdim,et al.  Mechanism of 6-hydroxydopamine neurotoxicity. , 1997, Journal of neural transmission. Supplementum.

[29]  G. Paxinos,et al.  The Rat Brain in Stereotaxic Coordinates , 1983 .

[30]  C. Sachs,et al.  Mechanisms of action of 6-hydroxydopamine. , 1975, Biochemical Pharmacology.