Perinatal exposure to delta-9-tetrahydrocannabinol (THC) alters goal-directed behavior and dopamine functioning in wistar rats.

Perinatal exposure to THC, the psychoactive component of cannabis, reduces motivation to work for rewards in adult rats, especially males, without affecting impulsive behavior. Rats exposed to 5 mg/kg/day THC from before birth through early nursing showed fewer lever presses and earned fewer reinforcers in tasks requiring high effort. The exposure did not alter baseline dopamine release in brain reward regions but dampened the dopamine response to cocaine in the nucleus accumbens. These findings suggest that prenatal cannabis exposure may produce an amotivational state by devaluing rewards rather than by impairing impulse control, with males more affected.

Study at a glance

Abstract

Cannabis use during 2021pregnancy 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 cannabis exposure to externalizing behavior in offspring. 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 and impulsivity in adult offspring perinatally exposed to THC. Dams were orally exposed to 0 or 5 mg/kg/day THC daily from 14 days prior to breeding to postnatal day (PND) 14. Differential reinforcement of high rates (DRH) and differential reinforcement of low rates (DRL) of responding tasks were used to examine motivation and impulsive action. We also measured dopamine (DA) functioning in the medial prefrontal cortex (mPFC) and nucleus accumbens (NAc) via in vivo fixed potential amperometry in littermates of rats that completed behavioral testing. Perinatal THC exposure had minimal effects on impulsive action measures during DRL 15s. Rather, perinatal THC exposure decreased DRL 15s burst responses and completed trials in both sexes, and reinforcers earned in THC-exposed males. Decreased lever presses during DRH were observed in both sexes perinatally exposed to THC, as well as fewer reinforcers in THC-exposed males. 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 can decrease motivation to work for reinforcers during high-effort tasks, that this effect may be more pronounced in males, and that the "amotivational state" resulting from perinatal THC exposure may be due to reinforcer devaluation.