October - December 2009, Volume 5, Issue 4

Ciobica A, Hritcu L, Artenie V, Stoica B, Bild V

Effects of 6-OHDA infusion into the hypothalamic paraventricular nucleus in mediating stress-induced behavioural responses and oxidative damage in rats

Acta Endo (Buc) 2009, 5 (4): 425-436
doi: 10.4183/aeb.2009.425

The stress response is mediated by the hypothalamo-pituitary-adrenal (HPA) system.\r\nActivity of the hypothalamic paraventricular nucleus (PVN) forms the basis of the HPAaxis.\r\nBehavioral and endocrine responsivity to threat and their ontogenetic changes may be\r\nmediated by PVN.\r\nMethods. 6-hydroxydopamine (6-OHDA) remains the most widely used substance in\r\nanimal models for inducing highly reproducible brain lesions. In our study, parvocellular neurons\r\nfrom the PVN of male Wistar rats were chemical lesioned by right-unilateral stereotaxic injection\r\nof two different doses of 6-OHDA (8μg/3μl and 16μg/3μl) and were subjected to a battery of\r\nbehavioral tests designed to assess spatial memory formation (radial arm-maze task) and anxiety\r\n(elevated plus maze). Further, we were interested in knowing whether a 6-OHDA lesion of the\r\nPVN would result in an imbalance in neuronal oxidative stress levels.\r\nResults. 6-OHDA-induced PVN lesions significantly increased the number of\r\nworking memory errors, suggesting effects on short-term memory, without affecting longterm\r\nmemory, explored by number of reference memory errors in radial arm-maze task. In\r\nelevated plus maze measuring anxiety, 6-OHDA significantly diminished anxiety-like\r\nbehavior in a dose-dependent manner. In addition, the neurotoxin induced a reduction in\r\nsuperoxide dismutase (SOD) and glutathione peroxidase (GPX) specific activities, while\r\nmalondialdehyde (MDA) level was found increased in the temporal lobe of rat brain, the\r\nmost vulnerable cortical area to oxidative stress effects.\r\nConclusion. Results suggest that 6-OHDA lesion of the PVN affects behavioral\r\nperformance via interactions with systems governing arousal level and possibly by\r\nincreasing neuronal oxidative stress.

Keywords: hypothalamic paraventricular nucleus, 6-hydroxydopamine, memory, anxiety-like behavior

Correspondence: Veronica Bild, PharmD, PhD, Lecturer, Pharmacology Dept, Faculty of Pharmacy, “Gr. T. Popa” University of Medicine and Pharmacy, 16, Str. Universitatii, Iasi, 700115,\r\nRomania, E mail: wbild@fiziol.umfiasi.ro