Effects of local infusions of dopaminergic drugs into the medial prefrontal cortex of rats on latent inhibition, prepulse inhibition and amphetamine induced activity

Impaired ability to 'gate out' sensory and cognitive information is conside red to be a central feature of schizophrenia and is manifested, among other s, in disrupted prepulse inhibition (PPI) and latent inhibition (LI). The p resent study investigated in rats the effects of increasing or decreasing d opamine (DA) receptor activation within the medial prefrontal cortex (mPFC) by local administration of the indirect DA receptor agonist amphetamine (A MPH; 10.0 mu g/side) or the DA antagonist cis-flupenthixol (FLU; 12.0 mu g/ side) on PPI and LI as well as on systemic AMPH-induced activity. The effec ts of intra-mPFC apomorphine (APO; 10.0 mu g/side) on PPI were also tested. AMPH infusions decreased systemic AMPH-inddced increase in locomotor activ ity in the open held, whereas FLU infusion was ineffective. Both infusions had no effect on LI and PPI. However, APO infusions induced a disruption of PPI. These results provide additional evidence that the mPFC is a componen t of the neural circuitry mediating PPI but plays no role in LI. In additio n, they show that the behavioral outcomes produced by DA receptor activatio n/blockade in the mPFC of the rat cannot be explained by postulating a simp le reciprocal relationship between the cortical and subcortical DA systems. (C) 2000 Elsevier Science B.V. All rights reserved.