A UPV/EHU researcher, who has had a long trajectory in the study of autism and the relationship between oxytocin and this condition, has participated in a piece of research that has served to demonstrate that the release of oxytocin leads to an increase in the production of anandamide, which causes mice to display a preference for interacting socially. This new mechanism by which oxytocin could be involved in social behaviour has been published recently in the prestigious scientific journal PNAS.
The researcher Olga Peñagarikano, a Ramón y Cajal researcher in the Department of Pharmacology at the UPV/EHU's Faculty of Medicine, and who has broad experience in the study of the neurobiological causes of autism and intervention in the oxytocin system as a potential treatment for this condition, has contributed towards a piece of research carried out by a team at the University of California, Irvine.
The Autism Spectrum Disorder (ASD) is mainly characterised by a deficit in social behaviour. Oxytocin, a natural hormone produced by the brain, is involved in social behaviour. There have been some clinical trials with humans in which it has been demonstrated that when the amount of oxytocin is increased, there are certain aspects that improve in social interactions. "Today there is as yet no treatment in autism to improve social behaviour, but one of the most promising therapies for ASD is intervention in the oxytocin system," explained the researcher.
It is believed that at least some of the patients with ASD could have a dysfunction in this system. In fact, in another recent publication, the researcher showed that a mouse autism model displayed reduced levels of oxytocin in the brain and that the administering of the hormone improved social behaviour. To do this, she built a viral vector —a virus that has been modified so that it is not pathogenic, in other words, it does not cause any illness— to transfer an artificial receptor to the neurons that produce oxytocin in the mouse. This technique, known as DREADD (Designer Receptors Exclusively Activated by Designer Drugs), is a widely used technique in the study of neuronal circuits: it consists of transferring an artificial receptor to the relevant neurons, which will be activated or disabled exclusively through the administering of a specific drug to study the effect.
Anandamide increases the preference for interacting socially
Dr Daniele Piomelli, a researcher at the University of California and expert in endocannabinoids, contacted Peñagarikano to be able to use the vector developed by this Basque researcher in the DREADD technique in a study that has served to demonstrate that the release of oxytocin leads to an increase in the production of anandamide (an endogenous substance produced by the body and which acts on the cannabinoid receptors, the same receptors on which cannabis acts). "My involvement in this work was to share the viral vector needed for the DREADD technique and to supervise its use and offer advice to ensure that it was used successfully," explained Peñagarikano.
The results obtained in the research suggest that one of the mechanisms by which oxytocin causes interpersonal relations to be perceived as pleasant could be through the release of anandamide. When the amount of anandamide was increased, the mice displayed a greater preference for interacting socially. When the oxytocin system is activated, both pharmacologically and through the DREADD technique, an increase in anandamide production occurs. Oxytocin is known to interact with other neurotransmitters in this system, such as serotonin and dopamine. This piece of work "reveals a new component in the system," concluded Peñagarikano, "which could have implications when it comes to developing drugs for conditions affected by impairments in social behaviour, such as autism, and based on the modulation of this circuit".
Dr Olga Peñagarikano (Tolosa, Basque Country, 1974) recently (2015) joined the Department of Pharmacology at the UPV/EHU Faculty of Medicine as a Ramón y Cajal researcher. She spent 6 years working at the University of California, Los Angeles (UCLA) as a post-doctoral researcher. Her work focusses on studying the neurobiological causes of autism in order to come up with treatments, and right now she is exploring intervention in the oxytocin system as a potential treatment for autism in a project being funded by the Brain and Behavior Research Foundation in the United States (formerly NARSAD).
Don Wei, DaYeon Lee, Conor D. Cox, Carley A. Karsten, Olga Peñagarikano, Daniel H. Geschwind, Christine M. Gall, Daniele Piomelli. "Endocannabinoid signaling mediates oxytocin-driven social reward". PNAS. Published online before print on October 26, 2015.
Image: Olga Peñagarikano, a Ramón y Cajal researcher in the Department of Pharmacology at the UPV/EHU's Faculty of Medicine