Rats exposed to the toxin methylazoxymethanol acetate (MAM) before birth or to THC shortly after birth showed adult behaviors resembling schizophrenia, such as social withdrawal and memory problems, along with increased expression of cannabinoid and dopamine receptor genes in the prefrontal cortex linked to DNA methylation changes. Giving THC during adolescence impaired social behavior in otherwise healthy rats but did not worsen the schizophrenia-like traits in rats already exposed to THC after birth. In rats exposed to MAM before birth, adolescent THC paradoxically reversed their memory deficit by altering dopamine receptor gene expression. The effects of adolescent THC exposure appear to depend on individual differences in dopamine signaling.
Prenatal exposure to THC, the main psychoactive component of cannabis, disrupts spatial memory and alters the balance of excitatory and inhibitory signaling in the hippocampus in a sex-specific manner. In adolescent male rats, THC exposure impaired memory retrieval and flexibility, reduced the density of a key type of inhibitory interneuron (CCK-positive basket cells), and increased markers of neuroplasticity. In females, memory retrieval was delayed but flexibility was spared, and the density of those inhibitory interneurons increased. The findings suggest male offspring are more vulnerable to prenatal THC's effects on memory processing, with sex-specific changes in synaptic plasticity and excitatory/inhibitory balance.