Let’s talk about a time you may wish you could forget: adolescence.
Saying adolescence is complicated would be an understatement. But what about the long-term consequences of our short-sighted decisions? You see, adolescent experiences–such as drug use–can alter and shape maturation of the dopamine pathway, an important neural pathway for addiction and reward, and lead to long-term dysfunction.
Hi. My name is Christina and I study how the stimulant amphetamine differentially impacts development of the decision-making part of the brain in the biological sexes.
Like much of the scientific literature, most previous work was done in males, thereby essentially overlooking roughly half the population for fear of “complicated hormone cycles”. Ah, men. Nevertheless, work in our lab with male mice showed that recreational-like doses of amphetamine in early adolescence, but not later, can result in complex changes to brain cells as they’re growing. These changes induce targeting errors, essentially rerouting some brain cells to target other regions and disrupting local circuitry. My work explores whether this phenomenon also occurs in female mice, using a 3-pronged approach involving molecular, neuroanatomical, and behavioural analyses.
Now, imagine that you are a growing cell in the brain–a neuron–trying to navigate to your target. How do you know where to go and how to get there? As humans, we use maps to navigate our complex cities. But what do neurons do? Well, they can recognize various molecules in their environment that serve to“guide” them along their journey. Like a giant game of hot and cold, these neurons sense the attractive (hot) and repulsive (cold) cues, using those signals to navigate to their targets.
Remarkably, these dopamine brain cells are still growing to their final targets during adolescence. As such, they are extremely vulnerable to environmental influences (like drug use). In fact, amphetamine exposure essentially disorients some of these neurons, causing them to “reroute” past their original target and into the frontal, decision-making part of the brain. Once there, they have a hard time making connections with their new neighbors, the result being increased impulsivity in adulthood–a hallmark of addiction.
So, sounds like it’s all figured out, right? Enter: female mice. My work shows that, incredibly, amphetamine exposure in neither early- nor mid-adolescence results in any of the structural or functional impairments observed in males. To try to unravel this protective mechanism, I am further investigating the role of puberty and pubertal hormones during this vulnerable window of dopamine development.
In sum, my work serves as a critical step in gaining an understanding of the biological basis of sex differences in how drugs of abuse affect the developing brain. Addiction is notoriously pervasive and difficult to treat. So it is imperative to understand the underlying mechanisms of the disease (and yes–it is a disease) in order to effectively develop more targeted treatments. In essence, I (like most humans) am still trying to understand women. Thank you for your attention.
By: Christina Popescu