A HISTOCHEMICAL-DEMONSTRATION OF ALTERED CYTOCHROME-OXIDASE ACTIVITY IN THE RAT-BRAIN BY NEUROLEPTICS

Regional alterations in neuronal functional activity were examined in the rat brain using cytochrome-c oxidase (COX) histochemistry followin g chronic neuroleptic treatment. Haloperidol, fluphenazine, and clozap ine were administered to animals for 28 days after which profiles of C OX activity were generated. Significant increases in COX activity were evident in area 2 of the frontal cortex of all treated animals. Cloza pine and fluphenazine, but not haloperidol, caused significant increas es in COX activity in the caudate nucleus, nucleus accumbens, septum, and pontine nucleus. Statistically significant increases in COX activi ty were also observed in hippocampal CA2 and CA3 subfields in clozapin e treated animals. Results offer support for the concept that neurolep tics achieve their therapeutic effects primarily via an enhancement of brain function in the frontal cortex, but also point to other brain r egions which may be involved in the actions of these drugs. (C) 1998 E lsevier Science B.V./ECNP.