A Ticking Clock
What kind of havoc does cocaine wreak on the biological clock from prenatal development to old age?
That’s the question that keeps Irina V. Zhdanova awake at night. An associate professor of anatomy and neurobiology who runs the Laboratory of Sleep & Circadian Physiology, Zhdanova is currently studying the effects of cocaine exposure in zebrafish from prenatal development through old age (the lifespan of the fish is about six years). Because thousands of human babies have been exposed in utero to cocaine and other illicit drugs, understanding how to reverse the drug’s effects has significant implications for clinical practice.
“Drug use is so pervasive today, and its effect on babies in utero is not well understood,” says Zhdanova. “It’s important to start understanding the effects of cocaine from the beginning.”
Her research with post-doctoral student Eva H. Shang on prenatal cocaine exposure, published in Physiology & Behavior, targets the body’s biological clock, and suggests that melatonin, a hormone produced by the pineal gland in the brain, may have a therapeutic role to play in counteracting the effects of cocaine on prenatal development. Further studies are needed, she says, to determine the potential effects of melatonin and whether the hormone can safely be administered during embryonic development.
Melatonin, with its strong antioxidant effects, maintains the body’s circadian rhythm or biological clock. It helps to control sleep, blood pressure, and the release of female reproductive hormones, among other bodily functions. The body produces melatonin exclusively at night, and if you have ever experienced jet lag it’s because your body’s melatonin production is disrupted when you are exposed to too much light in the evening.
Zhdanova and Shang’s research on zebrafish, a diurnal vertebrate whose sleep cycle mirrors humans (unlike mice and rats, who are nocturnal), is revealing—literally, because zebrafish are transparent. Their offspring hatch in approximately 50 hours, and within two to three days, they are actively hunting for food. When researchers add small amounts of water-soluble cocaine to the water, adult zebrafish receive it through their gills. In younger fish, it is absorbed through their translucent skin. “We can see how the brain develops, whether some brain areas grow faster than others,” she notes.
According to Zhdanova, cocaine exposure changes the zebrafishes’ pattern of brain development, affects the expression of biological clock genes, and alters melatonin signaling, growth, and transmission. She also found that prolonged exposure to the drug can disrupt neuron development.
“Drug use is so pervasive today, and its effect on babies in utero is not well understood. It’s important to start understanding the effects of cocaine from the beginning.” Irina V. Zhdanova
Another, gender-specific study with colleague Marcos A. López-Patiño and others, on cocaine withdrawal, which produces long-lasting behavioral effects and anxiety, determined that female zebrafish develop anxiety earlier than males, but the anxiety-like state is more persistent in males.
“Many drug users going through withdrawal are not looking for a high. They are suffering because they don’t have the drug. That’s why we’re interested in what happens with withdrawal. We don’t understand why they suffer.”
Zhdanova’s current research with zebrafish is focused on aging, and may have particular relevance for baby boomers, many of whom have experimented with drug use. “I want to know whether this earlier drug use contributes to the disorders they are experiencing later in life,” she says.