When presented with two levers, laboratory rats that were exposed to cannabis in utero were able to learn to push the one below the lightbulb that lit up. But the animals struggled to adjust their strategy when the rules of the game changed, for example, when they received a sugar reward when they pushed only the left or right lever regardless of the lightbulb. Rats born to mothers who had not inhaled cannabis were better able to learn the new strategy.
The results, presented yesterday (November 4) at the annual Society for Neuroscience conference, are “indicative of an inability to acquire and maintain a new strategy” following fetal cannabis exposure, says Hayden Wright, a PhD student in Ryan McLaughlin’s lab at Washington State University. Understanding such effects is critical as marijuana becomes legalized across the US, he adds. “As states allow more access, there has been an increase in self-reported cannabis use during pregnancy.”
Most studies of cannabis exposure in rodents have used injections of purified THC, the psychoactive ingredient in the drug, and the results are therefore hard to translate to humans who smoke marijuana, which contains more than 100 other active cannabinoids, Wright says. So the McLaughlin lab developed an experimental system that vaporizes cannabis extract into a glass enclosure where rats can be kept for variable periods of time.
For the current study, the researchers placed female rats in the chamber for two one-hour sessions per day throughout mating and gestation. During these sessions, the animals were exposed to cannabis-free vapor or vapor that contained high or low levels of the drug. The offspring of these rats were then tested for their ability to learn a simple lever-pressing task at two-months old.
The rat pups were presented with two levers. First, the researchers trained the animals to press the lever near a light. Then, the team switched it up, requiring the animals to always choose the left or the right lever, regardless of which light lit up, to receive a sugar reward. Finally, the researchers switched which lever was associated with the reward. While the rats whose mothers had been exposed to vapors with high levels of cannabis were just as good as the animals in the low-dose or no-cannabis treatment groups at learning the initial task, they made more errors in the second two parts of the behavioral test, regressing to the original strategy or even choosing the wrong lever when the light wasn’t lit.
The results do not suggest a general learning disability, McLaughlin notes, but a specific deficit in their ability to switch strategies. And the underlying mechanisms are still unclear, he adds. It could be that early exposure to cannabis disrupts the endocannabinoid system that is critical to many biological functions. Alternatively, the rats may suffer from changes in dopamine signaling in the brain, particular in the nucleus accumbens, where researchers have linked a drop in dopamine receptor expression to fetal cannabis exposure in rodents and humans.
“It’s still a very early story; these data are preliminary,” McLaughlin tells The Scientist. “But we think we might be onto something.” The researchers plan to look for differences in gene expression and protein levels in the nucleus accumbens and other brain areas to try to pinpoint the physiological changes that underlie the behavioral effects.