Morphine Perinatal Exposure Induces Long-Lasting Negative Emotional States in Adult Offspring Rodents

Abstract

Psychoactive substances during pregnancy and lactation is a key problem in contemporary society, causing social, economic, and health disturbance. In 2010, about 30 million people used opioid analgesics for non-therapeutic purposes, and the prevalence of opioids use during pregnancy ranged from 1% to 21%, representing a public health problem. This study aimed to evaluate the long-lasting neurobehavioral and nociceptive consequences in adult offspring rats and mice exposed to morphine during intrauterine/lactation periods. Pregnant rats and mice were exposed subcutaneously to morphine (10 mg/kg/day) during 42 consecutive days (from the first day of pregnancy until the last day of lactation). Offspring were weighed on post-natal days (PND) 1, 5, 10, 15, 20, 30, and 60, and behavioral tasks (experiment 1) or nociceptive responses (experiment 2) were assessed at 75 days of age (adult life). Morphine-exposed female rats displayed increased spontaneous locomotor activity. More importantly, both males and female rats perinatally exposed to morphine displayed anxiety- and depressive-like behaviors. Morphine-exposed mice presented alterations in the nociceptive responses on the writhing test. This study showed that sex difference plays a role in pain threshold and that deleterious effects of morphine during pre/perinatal periods are nonrepairable in adulthood, which highlights the long-lasting clinical consequences related to anxiety, depression, and nociceptive disorders in adulthood followed by intrauterine and lactation morphine exposure.

Perigestational Opioid Exposure Alters Alcohol-Driven Reward Behaviors in Adolescent Rats

“…This relapse also had a trending increase as abstinence time increased, suggesting that females may be more susceptible to context-reinstatement behaviors when alcohol is present and when abstinence is prolonged. Negative affect, which is more prevalent in humans and rats exposed to perigestational opioids, is perpetuated by abstinence and can lead to relapse behavior (Bakhireva et al, 2019; Konijnenberg et al, 2016; Castro et al, 2022; Koob, 2020). Symptoms of negative affect produced through chronic stress, however, can lead to opposing reward-seeking changes.…”

Repeated Cycles of Binge-Like Ethanol Exposure Induces Neurobehavioral Changes During Short- and Long-Term Withdrawal in Adolescent Female Rats

“…Elevated plus maze is a wooden plus apparatus, elevated 50 cm from the floor, with opposite two closed arms (50 × 10 × 40 cm) and two open arms (50 × 10 × 1 cm), surrounding by 1 cm device protection to prevent animals fall validated for anxiety-like assessment [ 40 ]. Animals were individually placed in the center of the apparatus facing the enclosed arms, which freely exploratory activity for 5 minutes [ 41 , 42 ]. Percentual of open arms entries (% OAE) and open arms time (%OAT) were measured according to the formula [ OA ( E / T )/ OA ( E / T ) + closed arms entries − CA ( E / T )] × 100] [ 26 , 41 , 43 ].…”