Brain Basis for Female Addiction

Women tend to become addicted to drugs and relapse faster than men. In a study in the Journal of Neuroscience, Helen Scharfman and Teresa Miller write that high levels of estrogen--and its effect on a neural route to the hippocampus called the mossy fiber pathway-- may be responsible for this difference.

In work with rats, the researchers found that females in the high estrogen state of their menstrual cycle showed changes in the synaptic plasticity of neurons in the hippocampus. The hippocampus is key to associative learning, so the high levels of estrogen could make the association between the experience of using a mind-altering drug and the drug itself stronger. The authors theorize that makes women more prone to addiction. They noted that an earlier study found female rats were more easily trained at self-administering opiates than male rats.

On the positive side, the finding that estrogen has an impact on synaptic plasticity could also be used to find new ways to promote learning.

The researchers also investigated the role of two opioid receptors, Mu and Delta, on the plasticity process. Painkillers like oxycodone primarily target the Mu receptor. Using electron microscopy the researchers found that females at high estrogen states had about three times more Delta opioid receptors than males.

The evidence of sex differences in how people respond to opioids could also lead to the development of pain-killers that are less addictive, the researchers said.

The findings could also have implications for epilepsy and other seizure disorders, which are characterized by over-stimulated neurons. “Interestingly females develop epileptic seizures more rapidly in the kindling model of epilepsy, consistent with greater plasticity,” they wrote. “Our data suggest that Delta opioid receptors could play a role.”

Scharfman is a neuroscientist at the New York State Office of Mental Health’s works at the Nathan Kline Institute for Psychiatric Research in Orangeburg, NY.

Milner is a professor of neuroscience at the Feil Family Brain and Mind Research Institute at Weill Cornell Medical College.