Prenatal Methamphetamine Exposure Impairs Helping Behaviour in Male Offspring: The Possible Role of miR-223 and NLRP3 Inflammasomes in the Amygdala.

Abstract

The increasing prevalence of methamphetamine abuse among women, particularly pregnant females, is a global concern. Methamphetamine can readily cross anatomical barriers like the blood-placenta barrier and cause detrimental impacts on the growing fetus. The current research evaluated the effects of prenatal methamphetamine exposure on helping behaviour and neuroinflammatory cascade in the amygdala of male offspring. On the tenth day of pregnancy, female rats received either saline or methamphetamine (5 mg/kg) until delivery. Once the offspring reached 21 days of age, the male ones were sep arated from their mothers and housed with normal male rats. An empathy-like behaviour test, which measured helping behaviour towards the cage mate, was conducted. The expression levels of miR-223-3p, NLRP3, Caspase 1, and gasdermin D (GSDMD) were evaluated in the amygdala of male offspring. Moreover, interleukin-1β (IL-1β) protein level was measured. Findings of this study revealed that male offspring exposed to methamphetamine during pregnancy had impaired helping behaviour. At the molecular level, prenatal methamphetamine exposure decreased miR-223-3p and increased inflammasome signaling by raising the levels of NLRP3, caspase-1, and GSDMD along with IL-1β levels. These findings indicate that prenatal methamphetamine exposure impairs emotional behaviour and activates inflammasome pathway in the amygdala.