Kobra Bahrampour Juybari1, Gholamreza Sepehri2, Manzumeh Shamsi Meymandi3, Seyyed Sajjad Vakili Shahrbabaki4, Amirhossein Moslemizadeh4, Nima Saeedi5, Azadeh Aminzadeh5, Masoumeh Nozari2, Mohammad Khaksari6, Tahereh Haghpanah7, Hamideh Bashiri8. 1. Department of Pharmacology, School of Medicine, Semnan University of Medical Sciences, Semnan, Iran. 2. Neuroscience Research Center, Institute of Neuropharmacology, Department of Physiology and Pharmacology, Afzalipour School of Medicine, Kerman University of Medical Sciences, Kerman, Iran. 3. Pathology and Stem Cells Research Center, Kerman Medical School, Kerman University of Medical Sciences, Kerman, Iran. 4. Faculty of Veterinary Medicine, Shahid Bahonar University of Kerman, Kerman, Iran. 5. Department of Pharmacology and Toxicology, Faculty of Pharmacy, Kerman University of Medical Sciences, Kerman, Iran. 6. Endocrinology and Metabolism Research Center, Institute of Basic and Clinical Physiology Sciences, Afzalipour School of Medicine, Kerman University of Medical Sciences, Kerman, Iran. 7. Department of anatomy, School of medicine, Kerman University of Medical Sciences, Kerman, Iran. 8. Neuroscience Research Center, Institute of Neuropharmacology, Department of Physiology and Pharmacology, Afzalipour School of Medicine, Kerman University of Medical Sciences, Kerman, Iran; Sirjan Faculty of Medical Science, Sirjan, Iran.. Electronic address: h.bashiri@kmu.ac.ir.
Abstract
INTRODUCTION: The present study was designed to clarify the effects of resveratrol (RSV) on social behavioral alterations and nociceptive reactivity in valproic acid (VPA)-induced autistic-like model in female and male rats. METHODS: Pregnant Wistar rats were randomly divided in five groups. Animals received saline, DMSO, VPA, RSV and RSV + VPA. VPA was administered (600 mg/kg, i. p.) on embryonic day 12.5 (E12.5) and pretreatment by resveratrol (3.6 mg/kg, s. c.) was applied on E6.5 until E18.5. All offspring were weaned on postnatal day 21 and the experiments were done in male and female rats on day 60. Social interaction, hot plate and tail flick tests were set out to assess social deficits and pain threshold, respectively. Sociability index (SI), Social novelty index (SNI) and latency time were calculated as the standard indices of social behaviors and pain threshold, respectively. RESULTS: The results indicated that systemic intraperitoneal administration of VPA (600 mg/kg) significantly decreased SI and SNI in social interaction test (SIT) especially in male rats, indicating the social impairments caused by VPA. RSV (3.6 mg/kg, s. c.) reversed VPA-induced social deficits in male rats, but not in female group. VPA administration resulted in significant increase in latency time in the hot plate and tail flick tests in male rats, whereas it had no such dramatic effect in females. RSV administration in combination with VPA had no significant effect on latency time compared to the valproic acid group in male rats. It is important to note that RSV by itself had no significant effect on SI, SNI and latency time in female and male rats. CONCLUSION: It can be concluded that valproic acid produces autistic-like behaviors and increases pain threshold in male rats which may be ameliorated at least in part by resveratrol administration. Further studies are needed to elucidate the molecular mechanisms involved in valproic acid and resveratrol-induced effects.
INTRODUCTION: The present study was designed to clarify the effects of resveratrol (RSV) on social behavioral alterations and nociceptive reactivity in valproic acid (VPA)-induced autistic-like model in female and male rats. METHODS: Pregnant Wistar rats were randomly divided in five groups. Animals received saline, DMSO, VPA, RSV and RSV + VPA. VPA was administered (600 mg/kg, i. p.) on embryonic day 12.5 (E12.5) and pretreatment by resveratrol (3.6 mg/kg, s. c.) was applied on E6.5 until E18.5. All offspring were weaned on postnatal day 21 and the experiments were done in male and female rats on day 60. Social interaction, hot plate and tail flick tests were set out to assess social deficits and pain threshold, respectively. Sociability index (SI), Social novelty index (SNI) and latency time were calculated as the standard indices of social behaviors and pain threshold, respectively. RESULTS: The results indicated that systemic intraperitoneal administration of VPA (600 mg/kg) significantly decreased SI and SNI in social interaction test (SIT) especially in male rats, indicating the social impairments caused by VPA. RSV (3.6 mg/kg, s. c.) reversed VPA-induced social deficits in male rats, but not in female group. VPA administration resulted in significant increase in latency time in the hot plate and tail flick tests in male rats, whereas it had no such dramatic effect in females. RSV administration in combination with VPA had no significant effect on latency time compared to the valproic acid group in male rats. It is important to note that RSV by itself had no significant effect on SI, SNI and latency time in female and male rats. CONCLUSION: It can be concluded that valproic acid produces autistic-like behaviors and increases pain threshold in male rats which may be ameliorated at least in part by resveratrol administration. Further studies are needed to elucidate the molecular mechanisms involved in valproic acid and resveratrol-induced effects.