In many species, increasing serotonergic activity can reduce aggression and reverse dominance relationships. These effects may in part be mediated through interactions with the arginine vasotocin/vasopressin (AVT/AVP) system. We tested this hypothesis in a territorial coral reef fish, the bluehead wrasse (Thalassoma bifasciatum), by experimentally enhancing serotonergic neurotransmission, using the selective serotonin re-uptake inhibitor (SSRI) fluoxetine. Terminal phase (TP) males received 2 weeks of nightly intraperitoneal fluoxetine injections (6 microg/g body weight) and were then tested for their aggressive response to an intruder and killed to examine AVT phenotype in the preoptic area of the hypothalamus (POA), an area important to social behavior in fishes. Our previously published study demonstrated that fluoxetine-treated males are less aggressive [H.A.N. Perreault, K. Semsar, J. Godwin, Fluoxetine treatment decreases territorial aggression in a coral reef fish, Physiol. and Behav. 79 (2003) 719-724.]. Here, further study of these same fluoxetine-treated males shows approximately twofold lower AVT mRNA expression relative to saline-treated controls in all regions of the POA (all p< or =0.05) without any changes in AVT-ir soma size (all p>0.4). This study experimentally supports the hypothesis that behavioral effects of SSRIs may be mediated in part through interactions with the AVT/AVP system. These results parallel findings from rodents and humans and are consistent with an indirect neurosteroidogenic rather than a solely direct serotonergic mechanism for SSRI effects on the AVT/AVP system. Furthermore, they suggest that SSRI effects on neuroendocrine function may be best modeled in animals with sensitive stress responses such as those found in nondomesticated animals.