Submitted by Christopher D. Lewis on Monday, 11/16/2009, at 2:36 PM

Nitric oxide (NO) and serotonin are two signaling molecules that correlate to human aggression levels. Nitric oxide is a peptide hormone that is produced when the nitric oxide synthase (NOS) binds oxygen and arginine. The two NOS isoforms that create NO in this case are neuronal NOS (nNOS) and endothelial NOS (eNOS). Serotonin is a steroid hormone that is synthesized in the central nervous system (CNS) by the brain. Serotonin, or 5-hydroxytryptamine (5-HT), is created when the amino acid, tryptophan, combines with the chemical reactor, tryptophan hydroxylase. The 5-HT signaling molecule is transmitted in the body by the 5-hydroxytryptamine transporter (5-HTT).

Nitric oxide stimulates blood vessel dilation by activating guanylyl cyclase which creates cyclic GMP. Nitric oxide is very susceptible to change, reacts quickly, and has a half-life of less than five seconds. NO also mediates important physiological and behavioral functions. The structure of eNOS is a dimer found in the endothelial tissue of blood vessel linings that regulates blood pressure. The structure of nNOS is also a dimer found in neural tissue that is important for development and learning. Serotonin is a key neurotransmitter system involved in aggression and impulsivity. Serotonin’s functions include regulation of mood, appetite, sleep, memory, and learning.

NOS has two knockout gene forms, which are eNOS-/- and nNOS-/-. When eNOS-/- is present, mice had very little aggression in males and females. When nNOS-/- is present, male mice were more aggressive and female mice were much calmer. Serotonin has one knockout gene form, which is 5-HTT-/-. When 5-HTT-/- is present, the serotonin molecule will also be eliminated to create the knockout gene, 5-HT-/-. Without the 5-HTT present, 5-HT neurons will not be transmitted, which will cause a decrease in male aggression and an increase in female aggression.

There are several other factors that can facilitate aggression in a study.  The conditions and social interactions of the mice can determine factors such as serotonin and how it relates to aggressive behaviors. Increased amount of isolation caused a decrease in the production of serotonin (Valzelli and Bernasconi, 1979; Kempf et al., 1984; Rilke et al., 1998, 2001). Isolation is almost a necessary factor in causing the aggressive behavior to become present, however further studies would most likely have to be done. There proves to be a correlation of 5-HT and the NOS knockout genes because the 5-HT turnover is reduced in mice that have the nNOS-/- and have 5-HT receptor genes that do not function properly.  In regards to aggression, androgens tend to play a role in causing more aggression, and estrogen tends to directly interfere with serotonin binding. Sex steroid hormones interact with Serotonin to create a more likely outcome of aggression.