ELECTRICAL SENSITIZATION OF THE MESO-LIMBIC DOPAMINERGIC SYSTEM IN RATS - A PATHOGENETIC MODEL FOR SCHIZOPHRENIA

To study whether it was possible to modify mesolimbic dopaminergic act ivity by intermittent electrical stimulations (IES), 44 rats were eith er electrically stimulated or sham-stimulated in the ventral tegmental area (VTA) once daily for 70 days. This was done through chronically implanted intracranial electrodes. The intensity of electrical stimula tion was determined by the lowest current that elicited a definite mot or response. Stimulated rats demonstrated a significantly potentiated behavioral response after 70 stimulations. Seven months after IES rats still demonstrated an increased sensitivity to electrical stimulation s in the VTA. A new stimulation period only resulted in a modest addit ional fall in threshold values. There was a highly significant differe nce between the current needed to provoke a given response in sensitiz ed rats and in sham-stimulated rats. The behavioral response to stimul ation was suppressed both by the dopamine (DA) D2 receptor antagonists haloperidol and raclopride and by the DA D1 receptor antagonist SCH 2 3390. Furthermore, stimulated rats showed an enhanced response to stim ulation with amphetamine and to a lesser extent with apomorphine. Betw een stimulation periods sensitized animals demonstrated a reduced soci al interaction. In conclusion intermittent electrical stimulations of the VTA resulted in a syndrome characterized by a hypersensitive respo nse to electrical and pharmacological DA provocation combined with abn ormal social interaction. This animal model has points of resemblance with recent interpretations of the DA hypothesis for schizophrenia.