Modification of behavioral responses induced by electrical stimulation of the ventral tegmental area in rats.

To investigate the role of the ventral tegmental area (VTA), a source of the mesolimbic dopaminergic pathway, in paranoid psychosis, a detailed analysis of the behavioral responses induced by electrical stimulation of the VTA was made. Abnormal behavior induced by bilateral high-frequency stimulation of the VTA consisted of two components: forward locomotion and exploration. Similar responses were obtained when the nucleus accumbens (NAC) or prefrontal cortex (PFC) were stimulated. The expression of behavioral responses to stimulation was significantly attenuated by dopamine (DA) receptor or antagonists, such as haloperidol, YM-09151-2 and SCH23390. These results indicate that VTA stimulation causes a transient hyperdopaminergic state in the brain, that resembles psychostimulant-induced abnormal behavior. The effects of chronic administration of methamphetamine (MAP) on the behavioral responses to electrical stimulation of the VAT were also investigated. Although an acute administration of MAP did not affect the behavioral responses to electrical stimulation of the VTA, chronic treatment with MAP (for 2 weeks) caused a long-lasting reduction in the electrical threshold for the induction of abnormal behavior, compared with chronic saline-treated rats. It is suggested that a lasting enhancement in the behavioral response to stimulation of VTA neurons may contribute to the etiology of paranoid schizophrenia and amphetamine psychosis.