**10.1. Stress**

There is a great deal of translational overlap in the research areas where focus on AVP and OXT is most relevant, and this is especially true with the studies on the effects of stress. Exposure to acute and/or chronic stress is often a predictor of depression/anxiety, addiction relapse, and relationship difficulties. It is suggested that the most valuable paradigms for investigating the roles of AVP and OXT in depression, anxiety, or addiction involve exposure to chronic stress. The use of ethologically relevant stressors in animal models, such as social stress, is most likely to produce translationally consistent results (effects in animals which parallel clinical data). Many commonly used chronic stress protocols used in studies of AVP/OXT and depression and anxiety, such as chronic mild stress, do not use stressors associated with human disorders.

Behavioral Roles of Oxytocin and Vasopressin 65

The animal and human data on OXT support the hypothesis that this peptide hormone is also a valid target for novel maternal mood disorder treatments. An interesting implication in this area is that synthetic OXT is already commonly used to induce labor, yet little is known about how this treatment may affect maternal behavior and/or offspring. OXT or OXT antagonists may also be effective in treating melancholic depression and seasonal affective disorder. There are also interesting non-pharmaceutical interventions which can manipulate OXT levels, such as physical touch and modified birthing practices and procedures (cesarean sections and induced labor vs. natural childbirth). Greater collaboration between animal and clinical researchers will accelerate the development of safe and effective AVP and OXT targeted treatments for depression and anxiety disorders, including postpartum depression, seasonal affective disorder, and PTSD. Projects that involve consistent interactions between animal and clinical researchers throughout the developmental process will be most effective. Another potential therapeutic application of AVP and OXT is in relationship counseling. Both of these hormones are likely to be involved in the mechanisms of establishing and maintaining the social bond necessary for a strong and stable relationship. AVP and OXT targeted treatments may be effective in treating the adverse effects of chronic social conflict, or the effects of other chronic stressors, especially in

Both affiliative behavior and addiction are mediated through similar central reward pathways. Central OXT pathways are also altered by addiction. Endogenous OXT activity is suppressed by chronic drug use, and elevated brain OXT levels may attenuate the negative effects of withdrawal [211]. There is preliminary evidence that exogenous OXT is capable of inhibiting stimulant and alcohol self administration and it may prevent stress and priming induced relapse [212]. As with autism, OXT centered treatments may be a useful adjunct to behavioral cognitive techniques. For example, intranasal OXT may augment the positive

Levels of AVP mRNA increase in the amygdala during early withdrawal from cocaine [214], and the blockade of V1b receptors can block reinstatement in rodents [215]. In a rodent model of ethanol dependence, a V1b antagonist decreases excessive levels of ethanol self administration [216]. There is further evidence that AVP secretion is attenuated in response to social stress in the sons of alcohol dependent fathers, but it is unclear how these results relate to the risk of developing an addiction [217]. While data from humans is lacking, the involvement of AVP in the etiology of stress related depression and anxiety suggests that this hormone may be implicated in the long term effects of addiction and the mechanisms mediating relapse. V1b antagonism may be a productive translational target for not only

While current translational efforts with OXT and autism acknowledge that the effectiveness of intranasal OXT treatments may only be relevant to social behavior deficits, the animal

effects of extinction training for addiction [213] and/or reduce rates of relapse.

drug dependence, but addiction associated depression and anxiety as well.

combination with behavioral cognitive therapy.

**10.3. Addiction** 

**10.4. Autism** 

While the role of AVP in the endocrine stress response has been studied in detail at the animal level, the effects of stress on OXT are not as well known. Integrative investigations which include both AVP and OXT may indentify novel interactions between these behaviorally potent peptides. The most promising translational area may be PTSD. There is already evidence that male PTSD patients have high plasma AVP, aggression, depression and anxiety levels and similar behavioral effects have been associated with elevated AVP in animals. While it is difficult to separate the changes in depression and anxiety from impairments in social behavior, an increased focus on OXT in PTSD studies may provide insight on the social deficits in PTSD patients. Social bonds are often negatively impacted by exposure to chronic stress, and these bonds can have a positive buffering effect on the negative effects of chronic stress.

An indication of the potential value of social support can be seen in the cultural comparison of postpartum depression prevalence. Societies that have high levels of social support for mothers have low rates of depression, and cultures with low levels of support have much higher rates [208]. There is evidence that social support has protective effects in stress related mood disorders, and understanding the role of AVP and OXT in the positive effects of social support may help maximize the value of social support focused interventions.
