Perinatal Exposure to Delta-9-tetrahydrocannabinol (THC) Alters Goal-Directed Behavior and Dopamine Functioning in Wistar Rats

Cannabis use during pregnancy is common as many pregnant women consider cannabis as a safe way to alleviate symptoms associated with pregnancy because it is “natural”. However, clinical evidence links perinatal exposure to cannabis to externalizing behavior in offspring including impulsivity, hyperactivity, and substance use. In preclinical research, most studies focus on exposure to the psychoactive constituent of cannabis, delta-9-tetrahydrocannabinol (THC). THC is lipophilic allowing it to cross the placental barrier and be secreted in maternal milk, thereby exposing the fetus/neonate. We used operant procedures to measure motivation to work for rewards, impulsive action, and impulsive choice in adult offspring perinatally exposed to 0 or 5 mg/kg/day THC. Differential reinforcement of high rates (DRH) was used to assess motivation, differential reinforcement of low rates (DRL) was used to examine impulsive action and delay discounting (DD) was used to measure impulsive choice. We also measured dopamine (DA) functioning in the medial prefrontal cortex (mPFC) and in the nucleus accumbens (NAc) via in vivo fixed potential amperometry in littermates of rats that completed behavioral testing. Perinatal exposure to THC dramatically decreased responding for reinforcers during DRH in offspring of both sexes, decreased reinforcers earned and trials completed during DRL, but had no effect on impulsive choice as measured during DD. In addition, perinatal THC exposure did not alter baseline DA release in the NAc or mPFC, but did attenuate the dopaminergic response to cocaine in the NAc. These results suggest perinatal exposure to THC may decrease motivation to work for reinforcers and provide neurochemical support for the “amotivational state” resulting from perinatal THC exposure.