Question

Summarise the rationale and results of:

Ludwig, M., Tobin, V.A., Callahan, M.F., Papadaki, E., Becker, A., Engelmann, M. and Leng, G., 2013. Intranasal application of vasopressin fails to elicit changes in brain immediate early gene expression, neural activity and behavioural performance of rats.pp.655-667.

Kompier, N.F., Keysers, C., Gazzola, V., Lucassen, P.J. and Krugers, H.J., 2019. Early life adversity and adult social behavior: focus on arginine vasopressin and oxytocin as potential mediators. Frontiers in behavioral neuroscience, 13.

Parker KJ, Oztan O, Libove RA, Mohsin N, Karhson DS, Sumiyoshi RD, Summers JE, Hinman KE, Motonaga KS, Phillips JM, Carson DS. A randomized placebo-controlled pilot trial shows that intranasal vasopressin improves social deficits in children with autism. Science translational medicine.

Answer 1

Intranasal application of vasopressin fails to elicit changes in brain immediate-early gene expression, neural activity and behavioral performance of rats
The study was carried out to determine whether there is an effect of the drug vasopressin when administered intranasally. Vasopressin increases the neural activity of the brain by the increased expression of the Fos gene. The experiment is carried out with the animal model by administrating the vasopressin intranasally and intracerebroventricularly checked for the behavior parameters such as elevated plus maze test and open field test, social recognition memory. Blood samples were collected from these experimental rats and drug concentration is analyzed by radioimmunoassay. Electrophysiology studies were done to check the brain cell activity.

RESULT: From this experiment, it is concluded that the administration of vasopressin and oxytocin through the intranasal route does not increase the Fos expression, neural activity suggesting the failure of the drug to reach the brain. When administrated through the intracerebroventricular route, there is an increase in the Fos gene expression and neural activity. The reason for the failure of the drug to reach the brain is due to the blood-brain-barrier that restricts 95% of the protein to reach the brain and the drug concentration is low.

Early Life Adversity and Adult Social Behavior: Focus on Arginine Vasopressin and Oxytocin as Potential Mediators
This study helps to understand the effect of stress in the postnatal period on the expression of the arginine vasopressin and oxytocin. Arginine vasopressin, a neurotransmitter involves the action of increased blood volume, cardiac output, and arterial pressure. It also activates various other neurotransmitter releases thereby altering the physiological and behavioral functions of the brain. Oxytocin is released by the hypothalamus, promotes positive emotions and increases social interaction.
Results:
Various animal studies show that exposure to stress leads to aggressive behavior. When analyzed, there is a decrease in the level of arginine vasopressin and oxytocin. Social recognition is also greatly reduced in these affected animals. Stress alters the expression of vasopressin and oxytocin in the lateral septum, Bed Nucleus of the Stria Terminalis and Nucleus Accumbens of the brain. A decrease in the arginine vasopressin and oxytocin greatly affects the social behavior of these animals. Thus, exposure to stress during the prenatal period will alter the behavior of the animal by decreasing the arginine vasopressin and oxytocin level.

A randomized placebo-controlled pilot trial shows that intranasal vasopressin improves social deficits in children with autism
Vasopressin, a neuropeptide plays a major role in social interaction. Social impairment affects the quality of life in children suffering from autism spectrum disorder. A double-blind, randomized placebo study was carried out in ASD patients by treating with intranasal vasopressin administration. Children received 24-32 IU daily dose of arginine vasopressin.
RESULTS:
Administration of arginine vasopressin in these patients showed a decrease in the anxiety level and repetitive behaviors. There is an increase in the score of the social responsiveness scale. This suggests that arginine vasopressin can be used to treat social impairments in children with autism.