Brain dopamine receptor plasticity: testing a diathesis-stress hypothesis in an animal model

Abstract

 A wealth of clinical data supports a major role of genetic liability as well as of altered brain dopamine (DA) functioning in different types of behavioural disturbances. Genetic influence on behaviour involves multiple genes, rather than one or two major genes, as well as non-genetic sources of variance. Thus, in recent years, increasing attention has been devoted to the involvement of stressful experiences (life events) in the development and expression of psychopathology. Moreover, a diathesis-stress hypothesis has been proposed, which suggests that the environmental factors (stress) are not specific for a given pathology, whereas genetic factors (diathesis) are. Results obtained in an animal model offer support to this hypothesis. Indeed, mice of the C57BL/6 and DBA/2 inbred strains are equally susceptible to stress but develop different behavioural disturbances related to different alterations of brain DA receptors. Moreover, quantitative trait loci (QTL) associations in the C57 (B) × DBA (D) recombinant inbred (RI) strains indicate a number of provisional QTLs influencing the behavioural effect of stress. Finally, the results of this analysis suggest the involvement of regulatory factors related to stress response and neural or synaptic plasticity in the control of brain DA receptor plasticity.