Target identification and validation in brain reward dysfunction

Addictive disorders (substance-use disorder and gambling disorder) are collected together in the fifth edition of The Diagnostic and Statistical Manual of Mental Disorders (DSM-5) partially because of a common brain origin, which seems to involve dysfunction of the reward system. Beyond these disorders, other neuropsychiatric diseases also share abnormal reward sensitivity, maladaptive impulsivity or compulsive behaviours, and have been reunited under the 'reward deficiency syndrome' (RDS) umbrella. Research in this field could then provide novel drugs with positive actions in all these diseases, but many animal models used for this purpose lack enough translational value to enable the identification of novel targets and should be then avoided. As we discuss here, only selected protocols could provide reliable targets that would be common to the whole family of diseases, thus qualifying for further validation in patients.