Neurobiology of social interaction as an alternative to drugs of abuse

The use of addictive drugs has constantly increased over the last decades especially among young people and represents a serious social and public health problem. Helping the substance dependent individual reorient his/her behaviour toward non-drug-related alternative activities has remained one of the greatest challenges in the therapy of drug dependence. Using animal models, it has been demonstrated that social interaction, if made available together with a drug of abuse, may aggravate drug dependence. However, little research has investigated the possibility that social interaction can have positive effect if offered as an alternative to drug taking. Here, we propose to use a vertical approach ranging from the behavior to the gene in order to determine how social interaction could be beneficial against drug dependence at the behavioral, neurochemical and molecular level. We will use: (1) Behavioral model such as conditioned place preference paradigm (CPP) to study the influence of social interaction on cocaine CPP and compare cocaine CPP to social interaction CPP (2) Microdialysis to compare rewarding effects of cocaine compared to non drug or social interaction in targeted areas especially the nucleus accumbens (Acb) shell and core (3) Molecular and cellular techniques to investigate the neurobiology underlying the effects of social interaction: We plan to i. Compare the activation of the cholinergic interneurons in the Acb shell and core between rats trained to express CPP to cocaine or CPP to social interaction; ii. Compare the expression of the transcription factors DeltaFosB and pCREB in rats trained to express cocaine CPP then undergo an extinction with or without social interaction; iii. Determine if the activation of p38 MAPK is selective for drug ie cocaine in comparison to social interaction, investigate the effect of p38 inhibitor microinjected into the Acb shell or core on the CPP to cocaine vs social interaction, establish and compare CPP to cocaine vs CPP to social interaction in p38 beta KO mice; iv. For the first time in the drug addiction field, assess the implication of the nuclear matrix protein SATB2 in drug-induced plasticity.

We could show that animals prefer the contact with a conspecific over drug taking although they are dependent to drugs. We could also find that social contact with a playfellow can have anti-stress effects. These findings may have implications for therapeutic strategies to treat drug-dependent people. Some individuals that start to take drugs, when they experience the positive pleasurable feeling that drug gives, they repeat drug use. Some can really loose the control over taking it and subsequently loose social contact with family and also friends that dont take drugs. Drugs produce then long lasting changes in the brain and these individual become dependent. Here we study how positive social interaction if offered as an alternative can protect against drug dependence. For that, rats can learn to associate pleasurable effect of the drug with an environment, and a neutral feeling with another environment. When the animals were allowed to choose between the environments, they will prefer the one where they got drugs. That is called conditioned place preference (CPP) to drugs. If, we give them the opportunity to spend time with a playfellow in the previously neutral environment without giving them any drugs, they preferred the playing environment over the one that was linked to drugs. Furthermore, even if they receive the drug again in the drug associated environment, they still prefer the place where they experienced social contact and play! We showed that social interaction can reverse brain activation induced by drugs and change the expression of markers previously modified by repeated drug taking.