Advancing schizophrenia drug discovery : optimizing rodent models to bridge the translational gap

Although our knowledge of the pathophysiology of schizophrenia has increased, treatments for this devastating illness remain inadequate. Here, we critically assess rodent models and behavioural end points used in schizophrenia drug discovery and discuss why these have not led to improved treatments. We provide a perspective on how new models, based on recent advances in the understanding of the genetics and neural circuitry underlying schizophrenia, can bridge the translational gap and lead to the development of more effective drugs. We conclude that previous serendipitous approaches should be replaced with rational strategies for drug discovery in integrated preclinical and clinical programmes. Validation of drug targets in disease-based models that are integrated with translationally relevant end point assessments will reduce the current attrition rate in schizophrenia drug discovery and ultimately lead to therapies that tackle the disease process

On the interaction between drugs of abuse and adolescent social behavior

Rationale Social factors influence drug abuse. Conversely, drugs of abuse alter social behavior. This is especially pertinent during post-weaning development, when there are profound changes in the social repertoire, and the sensitivity to the positive and negative effects of drugs of abuse is altered. Objectives This study aimed to provide an overview of our current understanding of the interaction between drugs of abuse and juvenile/adolescent social behavior. Methods We first provide evidence that a characteristic form of juvenile and adolescent social behavior, i.e., social play behavior, has reinforcing properties and is affected by drugs of abuse. Next, social risk factors for drug use and addiction are described, including antisocial personality traits and early social insults. Last, we discuss research that investigates social influences on drug use, as well as the consequences of perinatal drug exposure on later social interactions. Results Social play behavior is highly rewarding in laboratory animals, and it is affected by low doses of opioids, cannabinoids, ethanol, nicotine, and psychostimulants. In humans, antisocial personality traits, most prominently in the form of conduct disorder, are a prominent risk factor for drug addiction. Preclinical studies have consistently shown altered sensitivity to drugs as a result of social isolation during post-weaning development. The social environment of an individual has a profound, but complex, influence on drug use, and perinatal drug exposure markedly alters later social interactions. Conclusions The studies reviewed here provide a framework to understand the interaction between drugs of abuse and adolescent social interaction, at the preclinical and the clinical level