Role of kappa opioid receptors in social interaction reward

Spending time with some friends that do not use drugs (positive social interaction) can be an efficient alternative to drug use. In animals, we can evaluate social pleasure or reward by measuring the social interaction preference where we put the rat in a chamber on one day with another rat partner from the same gender, age and weight; and the next day we put the rat alone in another different chamber. After 8 days, we let the rat prefer where he would like to spend more time. Social interaction preference is when the rat prefers to spend more time in the chamber where he got social interaction. We have recently found that social interaction preference can reduce a marker of stress (P38 activation) in a region of the brain implicated in reward and stress called the shell part of the nucleus accumbens. These effects of social interaction are considered anti-stress. In this project, we suggest that these anti-stress effects of social interaction preference are mediated by a reduction in kappa opioid receptors (KOR) activation in the ventral part of the nucleus accumbens shell leading to a reduction in P38 activation as shown previously and a reduction in aversive negative behaviors involved in stress. We also suggest that the rewarding effects of social interaction preference are mediated through an increase in the activation of kappa opioid receptors and the activation of another kinase involved in reward called ERK in the dorsal part of the nucleus accumbens shell. To test this hypothesis, we will inject KOR agonist and P38 inhibitor locally in the ventral nucleus accumbens shell and study the effects of the injection on social interaction preference. In addition, we will investigate ERK activation associated to social interaction preference in the dorsal nucleus accumbens shell using immunohistochemistry then we plan to inject KOR antagonist and ERK inhibitor locally in the dorsal nucleus accumbens shell. Then we will study the effects of KOR antagonist injection on social interaction preference and ERK activation in the dorsal nucleus accumbens shell using immunohistochemistry. This project will be the first investigating the implication of KORs in positive social interaction effects via two complementary mechanisms in the nucleus accumbens shell by lowering the stress in the ventral part and increasing the reward in the dorsal part. This knowledge will help in designing effective social strategies to prevent drug dependence and identifying new targets for the development of new medications for the treatment of drug addiction and other psychiatric diseases.

Spending time with some friends that do not use drugs (positive social interaction) can be an efficient alternative to drug use. Using animal models, we can evaluate social pleasure or reward by measuring the social interaction preference whereby we put the rat in a chamber on one day with another rat partner from the same gender, age and weight; and the next day we put the rat alone in another separate chamber. After 8 days, we let the rat choose where he would prefer to spend more time. Social interaction preference is when the rat prefers to spend more time in the chamber where he got social interaction. We have recently found that social interaction preference can reduce a marker of stress (P38 activation) in a region of the brain implicated in reward and stress called the shell part of the nucleus accumbens. These effects of social interaction are considered anti-stress. In this project, we hypothesized that these anti-stress effects of social interaction preference are mediated by a reduction in kappa opioid receptors (KOR) activation in the ventral part of the nucleus accumbens shell leading to a reduction in P38 activation as shown previously and a reduction in aversive negative behaviors involved in stress. We also hypothesised that the rewarding effects of social interaction preference could be mediated via an increase in the activation of kappa opioid receptors and the activation of another kinase involved in reward called ERK in the dorsal part of t he nucleus accumbens shell.