Prenatal alcohol and cannabis exposure can have opposing and region‐specific effects on parvalbumin interneuron numbers in the hippocampus.

Background: We recently showed that alcohol and cannabis can interact prenatally, and in a recent review paper, we identified parvalbumin‐positive (PV) interneurons in the hippocampus as a potential point of convergence for these teratogens. Methods: A 2 (Ethanol [EtOH], Air) × 2 (tetrahydrocannabinol [THC], Vehicle) design was used to expose pregnant Sprague‐Dawley rats to either EtOH or air, in addition to either THC or the inhalant vehicle solution, during gestational days 5–20. Immunohistochemistry was performed to detect PV interneurons in 1 male and 1 female pup from each litter at postnatal day 70. Results: Significant between‐group and subregion‐specific effects were found in the dorsal cornu ammonis 1 (CA1) subfield and the ventral dentate gyrus (DG). In the dorsal CA1 subfield, there was an increase in the number of PV interneurons in both the EtOH and EtOH +THC groups, but a decrease with THC alone. There were fewer changes in interneuron numbers overall in the DG, though there was a sex difference, with a decrease in the number of PV interneurons in the THC‐exposed group in males. There was also a greater cell layer volume in the DG in the EtOH +THC group than the control group, and in the CA1 region in the EtOH group compared to the control and THC groups. Conclusions: Prenatal exposure to alcohol and THC differentially affects parvalbumin‐positive interneuron numbers in the hippocampus, indicating that both individual and combined exposure can impact the balance of excitation and inhibition in a structure critically involved in learning and memory processes. [ABSTRACT FROM AUTHOR]