Dopaminergic sensitization of rats with and without early prefrontal lesions: implications for the pathogenesis of schizophrenia.

To study whether an early lesion of prefrontal cortex (PFC) would influence mesolimbic dopaminergic sensitization induced by intermittent electrical stimulation (IES) of the ventral tegmental area (VTA) or change social interactions in animals exposed to both electrical sensitization and prefrontal lesions, we examined the behaviour of rats with or without early prefrontal lesions following repeated electrical stimulation of the VTA. Additionally, we wanted to study the influence of immobilization stress on rats exposed to a combination of prefrontal lesion and daily restraint in Plexiglas tubes prior to IES. Neither early lesion of PFC nor repeated restraint influenced development of sensitization. However, the combination of early prefrontal lesion and IES resulted in changes in social interactions neither seen following IES nor in lesioned rats. The changes were most pronounced in the group exposed to both IES, prefrontal lesions and restraint. Furthermore, repeated restraint caused a significant increase in the threshold current for provocation of the behavioural response related to VTA stimulation (head stereotypies/sniffing). The implications of the findings for sensitization of the mesolimbic dopaminergic system as a model for development of schizophrenia are discussed.