Female vulnerability to drugs tied to estrogen, U-M researcher reports

November 14, 2001

SAN DIEGO---Estrogen may make the brain more vulnerable to addiction, with the effects of this heightened susceptibility persisting even in the hormone's absence, according to a University of Michigan study presented Nov. 14 at the 2001 meeting of the Society for Neuroscience in San Diego.

"Years ago, people said that women shouldn't smoke or drink because we were more likely to become addicted," says U-M biopsychologist Jill B. Becker, who conducted the research, which is funded by the National Institute on Drug Abuse (NIDA). "I'm a feminist and don't subscribe to old-school ideas that women are the 'weaker' sex in need of protection.

"Yet these new findings suggest that when it comes to drug use, women should be extremely cautious, especially younger women who may be experiencing major hormonal swings at just the same time in their lives when many of their peers are first experimenting with nicotine, cocaine and other addictive substances." Older women using HRT may also increase their vulnerability to drug addiction.

At the meeting, Becker will present new data from a series of studies on approximately 200 rats showing that female rats who received estrogen as well as cocaine over a period of three weeks exhibit 20 percent to 50 percent more "sensitization" than either female rats who did not receive estrogen or male rats. Sensitization was measured by quantifying repetitive movements of the head and forelimbs, and turning in circles.

Drug sensitization is thought to cause craving for a drug like cocaine, Becker notes. For example, rats who are sensitized after repeated drug doses learn to self-administer cocaine faster and at lower doses than other animals. These changes in behavior persisted after the female rats, all of whose ovaries had been surgically removed, stopped receiving estrogen, Becker reports.

"We know from other studies that sensitization to cocaine results in structural changes in the brain that persist for some time," Becker says, pointing to recent work by U-M colleagues Kent Berridge and Terry Robinson. (See http://www.umich.edu/~newsinfo/Releases/2001/Sep01/r092501b.html). "Our results suggest that estrogen not only affects the acute response to cocaine, but also intensifies the long-term changes that occur in the brain. These results are important for our understanding of the basic neural processes that lead to drug addiction, and for our understanding of why some individuals may be more at risk than others."

For many years, Becker explains, scientists have tried to determine how estrogen can produce all of the effects attributed to it, including mood swings, improvement in verbal abilities, decreases in spatial abilities, and enhanced sensory and motor functions, including lower thresholds for visual, olfactory and tactile stimuli and more rapid complex motor sequence abilities.

Recently, Becker and others have been examining the hormone's impact on neurotransmitters such as dopamine in two specific areas of the brain, the nucleus accumbens and the striatum. These brain areas are known to be important in behaviors such as eating, sex, and compulsive drug use.

"My lab has demonstrated that estrogen has rapid effects that boost the amount of dopamine released," says Becker. "These effects are evident in sexual behavior, as well as compulsive drug-seeking. Dopamine levels increase when a female rat is engaging in sexual behavior that she finds rewarding, and for female rats, not all sex is rewarding." Male rats apparently prefer intromission every 30 seconds, followed by rapid ejaculation, she reports, while females prefer a slower pace, with one or two minutes between intromissions. This pace activates a series of synaptic pathways in the female's brain that triggers the release of prolactins necessary for successful pregnancy.

In the wild, female rats run away from the mating male to slow down the pace to their desired level. In the laboratory, female rats will bar press to get away from the male, but most experimenters use a seminatural environment that gives the female a safe place to run away to and hide from the male. In experiments, Becker and colleagues have found that estrogen enhances the behaviors that females engage in to slow male rats down. "So, the effects of estrogen to enhance sexual motivation may underlie the effects of estrogen on drug sensitization and addiction," Becker speculates.

University of Michigan

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