Genes or sex hormones?

Oct 22, 2007 18:06 GMT  ·  By

We know that testosterone makes men aggressive and muscular, while female hormones turn women into protecting "mothers" but also more vulnerable to addictions. But a new Yale research shows that it's not all about hormones; genes too are involved in shaping the sex-related behavior and the females' proneness to addiction could be linked to genes located in the sex chromosomes.

"This is the first time that any behavior has been associated specifically with sex chromosomes independent of gonadal hormones," the lead author Jennifer Quinn of Yale University told AFP.

Female mammals (including women) are known for long to be more likely than males to get habit-forming behavior, including addiction. Sex-specific hormones, secreted by gonads, explain just partially the difference.

To check this, the research team created two engineered mice variants: one mouse with testicles but female sex chromosomes, and another with ovaries and male sex chromosomes, allowing the assessment of hormones and gene effects separately.

Mutant and normal male and female mice determined on their own which of the three side-by-side openings led to food. Within days, all the mice went directly to the correct door without hesitation.

The mice with XX chromosomes, both normal females, and mutant mice with testicles, learned the drill more rapidly, a first clue that genes could be behind the difference in habit formation between the sexes. After a period of nine days, half of each group was tested with "conditioned taste aversion", three daily injections of lithium chloride following each free meal, in a new location. "The drug makes the animals feel sick, causing them to shy away from food associated with that feeling. If you drink too much creme de menthe, in the future you may want to avoid anything that has a minty flavor. It is something humans experience all the time", said Quinn.

Two days later, the mice were tested to check if they went to the same hole where they found food during the training period. The two types of XX mice went straight to the right opening, while the XY mice acted worse.

The XX chromosome mice got stronger habits, but they were not connected to hormones. To strengthen their finding, the scientists repeated the tests after removing the mice's gonads.

The test was repeated with a longer training period of 15 days. This time, the XY mice displayed the same level of habit formation as females, pointing to a delicate tuning between rote behavior and goal-oriented action. "The study points in two directions for future research. We think the results may be applicable to addiction and its compulsive nature, but nobody has tested whether there is such a sex difference independent of hormones in a drug habit," said Quinn.

Previous studies revealed that mice became addicted more easily to alcohol than to sugar, and the team will check if females are more prone to this than males. The second interest is for a possible treatment for addiction. "So far, we have established that genes are involved independent of hormones, but we don't know yet which ones," Quinn said. Chemicals inhibiting those genes "could potentially revert someone from a habitual responder (addict) back to a goal-directed responder", she added.