Activation of the retrohippocampal region in the rat causes dopamine release in the nucleus accumbens: disruption by fornix section

There is a well-described projection from the retrohippocampus (subiculum a nd entorhinal cortex) to the nucleus accumbens that is involved in the cont rol of psychomotor behaviour, and is implicated in the aetiology of schizop hrenia Cortical abnormalities are widely reported in the brains of schizoph renic patients, but it is unclear whether they are the cause or consequence of those changes in subcortical systems that are treated with neuroleptic drugs. We have, therefore, conducted a series of microdialysis experiments in anaesthetized rats to determine whether infusion of the excitotoxin, N-m ethyl-D-aspartate, into the retrohippocampus increases mesolimbic dopamine release. We found a clear and reproducible increase in extracellular dopami ne in the nucleus accumbens following N-methyl-D-aspartate (2.5 mug), that was abolished when we sectioned the fimbria-fornix. Furthermore, inhibition of gamma -aminobutyric acid receptors following retrohippocampus administr ation of bicuculline (4 mug), also increased dopamine in the nucleus accumb ens. The dopamine response to bicuculline was accompanied by an increase in dopamine metabolism, was long lasting, and also reduced by fornix section. The response to both N-methyl-D-aspartate and bicuculline depends on the in tegrity of the pi-ejection from the retrohippocampus to the nucleus accumbe ns. The results provide an underlying mechanism whereby a primary insult in the temporal cortex, caused by excessive N-methyl-D-aspartate receptor sti mulation, can produce a hyperdopaminergic state. In addition, an increase i n subiculo-accumbens activity evoked by bicuculline may also explain why pa tients with limbic epilepsy can develop a psychosis. (C) 2000 Elsevier Scie nce B.V. All rights reserved.