Dopamine Activity in the Lateral Anterior Hypothalamus Modulates AAS-Induced Aggression through D2 but not D5 Receptors

Melloni, Richard H., Jr. & Schwartzer, Jared J. (2010). Dopamine activity in the lateral anterior hypothalamus modulates AAS-induced aggression through D2 but not D5 receptors. Behavioral Neuroscience, Vol 124 (5). doi: 10.1037/a0020899

The hypothalamus, as we learn in chapter 12, has a lot to do with generation of behavior. With roles in eating, drinking, sexual behavior, aggression, and many others, it is a small part of the brain that has a very active role.

Researchers in this study were interested in past research that shows the effects of increased aggression in teenagers using synthesized steroids (anabolic androgenic steroids). The anterior hypothalamus is a region with the function of controlling aggression. It connects to other hypothalamic and limbic nuclei. When teenagers take these AAS, the anterior hypothalamus produces more dopamine to combat the increased aggression. This increase in dopamine is localized in the nucleus circularis and the medial supraoptic nucleus. These two nuclei moderate the aggression through the lateral subdivision of the anterior hypothalamus.

There are two classifications of dopamine receptors: D1 receptors and D2 receptors. Both receptors are coupled with G-proteins. The two receptors produce opposite responses.  Activation of D2 receptors produces neural inhibition (by decreasing adenylyl cyclase). Activation of D1 receptors produces neural excitation (by increasing adenylyl cyclase).

Research has shown that some drugs have been effective on reducing aggression in mice by blocking D2 receptors, but they have negative side effects such as a decrease in motor control and a decrease in arousal.

Less is known about receptivity of D5 receptors to steroids. Researchers in this study used microinjection techniques to determine whether antagonism of the D2 or D5 receptors in the anterior hypothalamus suppresses adolescent aggression produced by anabolic androgenic steroids.

A sample of 108 male Syrian hamsters was used in the study. The hamsters were given daily subcutaneous injections of a steroid mixture consisting of testosterone cypionate, nandrolone decanoate, and boldenone undecylenate dissolved in sesame oil for 30 consecutive days during the time period of their adolescent development. This daily treatment design was to emulate a chronic use regimen. This type of study has showed increased aggression in 85% of a sample of hamsters. A small sample of hamsters was given an injection of sesame oil alone as a control.

Researchers implanted a cannula device into the hamsters heads, aimed at the anterior hypothalamus. This is what they used to stick the injection needle into the right area. After each injection, the hamsters were placed in their cages for ten minutes before they were tested for aggressive behaviors using the resident-intruder paradigm. During the testing, one hamster was put in a cage with another hamster. A composite aggression score was compiled for each hamster by observing the total number of attacks and bites during the test period (10 minutes). The researchers also measured any changes in motor activity across the ten minute time span.

To examine the D5 receptor expression, the researchers did not cannulate one set of hamsters. One day after that group’s behavioral testing, the animals were killed and their brains were removed, postfixed in a perfusion fixative and paraformaldehyde, and cryoprotected in a sucrose and saline solution overnight. Brain slides of the Lateral anterior hypothalamus were magnified and the cells were counted.

Results indicated that adolescent hamsters exposed to the steroids did show increased aggression. They committed more than five times the aggressive acts than the oil-treated control group. For the aggression control treatment, those hamsters given high doses had significantly less social contact with the “intruder” hamsters as opposed to those given the medium or low dose. Eticlopride, but not SCH-23390, modulated steroid-induced aggression without motor and social side-effects. Treatment with moderate doses of steroids in adolescence resulted in an increase in dopamine and the expression of D2 receptors. Researchers reported that D5 receptors’ function is still difficult to discern. It is not yet known if these receptors are involved in the aggression control, like the D2 receptors.