аЯрЁБс>ўџ 24ўџџџ1џџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџьЅСo@№ПYbjbj p p  ooпџџџџџџˆьььььььhhhh$Œ њ ЖЄЄЄЄЄЄЄЄI K K K K K K $А R ^o EьYЄЄYYo ььЄЄД ЕЕЕY„ьЄьЄI ЕYI Е(ЕнььнЄ˜ 0“LбчУhн:н5 Ъ 0њ н`ˆ`ньььь`ьнXЄ„(^Е†Lв‡ЄЄЄo o DD$ŸDALTERED NOCICEPTION IN THE EXPERIMENTAL MODEL OF ALZHEIMER S DISEASE; NOXA-DEPENDENT DIFFERENCES Melita `alkovi-Petriai, Ivana Ferber and Zdravko Lackovi Department of Pharmacology, Medical School and Croatian Institute for Brain Research, University of Zagreb, Šalata 11, 10 000 Zagreb, Croatia AIMS: Intracerebroventricular (icv) administration of low streptozotocin doses produces long-term and progressive deficits in cognitive behaviour and cerebral glucose and energy metabolism, resembeling those found in the brain of patients with Alzheimer’s disease. Therefore, streptozotocin icv treated rats have been proposed as an appropriate experimental model of sporadic Alzheimer’s dementia. We have investigated nociception in the streptozotocin icv (0.5 -1 mg/kg) treated rats during the eight week long post-treatment period. METHODS: Spontaneous pain threshold has been measured following the thermally-and mechanically-induced pain stimulus in the hot plate (55 ( 0.5oC) and the paw pressure test, respectively. RESULTS: Spontaneous pain treshold in streptozotocin icv treated rats following the thermally-induced pain stimulus demonstrated increased values d"25% in comparison to the respective controls within the observed period. Statistically significant increment was seen as early as two weeeks after the drug treatment, with plato values reached in the fourth week and a tendency of returning to the normal values afterwards. However, pain treshold following the mechanically-induced pain stimulus was decreased (-19 to -36%) in streptozotocin icv treated rats, in comparison to the controls, with decrement being statistically significant from the first to the eights week after the drug treatment. CONCLUSION: Streptozotocin icv treated rats that represent the experimental model of sporadic Alzmeir's disease have altered nociception that depends on the nature of pain stimulus, being different following&ˆŒ”Р+ 1 J e t x y z ž Љ М Р о ѕ   # > N Й Э н с є  . / @ A B іьтдіЪСЕЌЕЌСЌЕСЕСЕСЕЃЕС—Е‡w‡wgw‡wZ‡hЭ$6CJaJmH sH hz]Ÿh &Ё6CJaJmH sH hz]Ÿh7i%6CJaJmH sH hz]Ÿh~>r6CJaJmH sH hz]Ÿh7i%6CJaJhБ)6CJaJh ”6CJaJhz]Ÿhйе6CJaJhЭ$6CJaJht(ђCJmH sH hЙaрhЙaр6CJmH sH hј9ЉCJmH sH hь[CJmH sH hЙaрCJmH sH #Т: + C %єWXYїђэххххрлйgdt(ђgdt(ђ$a$gdz]Ÿgdt(ђgdt(ђ$a$gdt(ђ Y§B M R g y ‘ • И Щ Э Ю в г к я § џ F s t ’ВЖш№ђтвђТЕЉЕТ–Т„ТxoxfoZoЉZNENEhБ)6CJaJhz]Ÿhј9Љ6CJaJhz]Ÿhб8с6CJaJhЭ$6CJaJhЏ^‚6CJaJhz]Ÿh &Ё6CJaJ"hz]Ÿh &Ё6CJH*aJmH sH % jБ№hz]Ÿh &Ё6CJaJmH sH hz]ŸhЏ^‚6CJaJhЏ^‚6CJaJmH sH hz]Ÿh &Ё6CJaJmH sH hz]Ÿh~>r6CJaJmH sH hz]ŸhфЇ6CJaJmH sH hЭ$6CJaJmH sH №)Z#$2ЁВОСарє '(34OS™œŸйкђѓєѓчѓоѓоѓчечЩчЩРЩЗЕЩЊЩЗšš€sf€f€sšZhz]Ÿht(ђ6CJaJhЏ^‚6CJaJmH sH hbШ6CJaJmH sH hz]Ÿ6CJaJmH sH h ”6CJaJmH sH hz]Ÿht(ђ6CJaJmH sH hz]Ÿhz]ŸCJaJUh ”6CJaJhz]Ÿ6CJaJhz]Ÿhz]Ÿ6CJaJhЭ$6CJaJhЏ^‚6CJaJhz]ŸhЙaр6CJaJhz]Ÿhј9Љ6CJaJ" the thermal and mechanic noxa. Whether this effect is related to the specific and selective toxicity of streptozotocin for certain molecular structures or to the consequently induced cerebral neurochemical disorders, remains to be elucidated. Supported by the projects of the Croatian Ministry of Science and Technology (0108253 and 108134). єWXYі№ьht(ђ ht(ђCJht(ђ6mH sH А‚. 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