The Effects of Alcohol and Cannabinoid Exposure during the Brain Growth Spurt on Behavioral Development in Rats

Cannabis is the most commonly used illicit drug among pregnant women. Moreover, over half of pregnant women who are consuming cannabis are also consuming alcohol; however, the consequences of combined prenatal alcohol and cannabis exposure on fetal development are not well understood. The current study examined behavioral development following exposure to ethanol (EtOH) and/or CP-55,940 (CP), a cannabinoid receptor agonist. From postnatal days (PD) 4-9, a period of brain development equivalent to the third trimester, Sprague-Dawley rats received EtOH (5.25g/kg/day) or sham intubation, as well as CP (0.4 mg/kg/day) or vehicle. All subjects were tested on open field activity (PD 18-21), spatial learning (PD 40-46), and elevated plus maze (PD 30) tasks. Both EtOH and CP increased locomotor activity in the open field, and the combination produced more severe overactivity than either exposure alone. Similarly, increases in thigmotaxis in the Morris water maze were caused by either EtOH or CP alone, and were more severe with combined exposure, although only EtOH impaired spatial learning. Finally, developmental CP, but not EtOH, increased time spent in the open arms on the elevated plus maze. Overall, these data indicate that EtOH and CP produce some independent domain-specific effects, but many effects of EtOH and CP on behavior were additive. Importantly, these data suggest that combined prenatal exposure to alcohol and cannabis may be more damaging to the developing fetus, which has implications for the lives of affected individuals and families and also for establishing public health policy.