This study was performed to evaluate the effects of prenatal exposure to pregabalin (PGB) on behavioral changes of rat offspring in an animal model of valproic acid (VPA)-induced autism-like symptoms. Pregnant rats received VPA (600 mg/kg/i.p.) once at 12.5 gestational days for autism-like symptom induction in offspring. After the delivery single male and single female offspring from each mother were randomly selected for behavioral test (anxiety, pain response, pleasure, and motor function) at 60th day adulthood (n = 7). Offspring received prenatal PGB (15 & 30 mg/kg/i.p.) during gestational days 9.5 to 15.5 either alone or in combination with VPA (PGB15, PGB30, PGB15 + VPA, and PGB30 + VPA). Control offspring received normal saline during the same period. The result showed that prenatal VPA exposure was associated with autism-like behaviors in rat offspring. PGB treatment during the gestational period revealed significant reduction in sucrose preference test and anxiety in elevated plus maze and open field test in offspring. Also, PGB treatments exhibited a dose-dependent increase in pain threshold in prenatally VPA exposed rats in tail-flick and hot plate test. Also, there was a sex-related significant impairment in motor function in beam balance and open field test, and male rats were affected more than females. However, no significant sex differences in sucrose preference and pain sensitivity were observed in prenatal PGB-treated rat offspring. In conclusion, prenatal exposure to VPA increased the risk of autism-like behaviors in the offspring rats, and PGB treatment during the gestational period was associated with some beneficial effects, including anxiety reduction and motor impairment in autism-like symptoms in rat offspring. K E Y W O R D S anhedonia, anxiety, autism, pain, pregabalin, valproic acid | 501 SHAMSI MEYMANDI Et Al. 1 | INTRODUCTION Autism spectrum disorder (ASD) is a complicated, behaviorally defined disorder, including communication and social interaction deficits and restricted, repetitive and stereotyped behaviors (Bolte et al., 2019). Prevalence estimates and diagnosis rates of ASD have risen substantially in the last two decades reaching 1.5% in developed countries (Lyall et al., 2017). According to the World Health Organization (WHO) report in 2018, 1 in 160 children had ASD. In most of cases, ASD is associated with epilepsy, since different studies showed that 22% to 38% of children with autism also suffer from comorbid epilepsy (