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 following chronic neuroleptic treatment. Haloperidol, fluphenazine, and clozapine were administered to animals for 28 days after which profiles of COX activity were generated. Significant increases in COX activity were evident in area 2 of the frontal cortex of all treated animals. Clozapine and fluphenazine, but not haloperidol, caused significant increases in COX activity in the caudate nucleus, nucleus accumbens, septum, and pontine nucleus. Statistically significant increases in COX activity were also observed in hippocampal CA2 and CA3 subfields in clozapine treated animals. Results offer support for the concept that neuroleptics achieve their therapeutic effects primarily via an enhancement of brain function in the frontal cortex, but also point to other brain regions which may be involved in the actions of these drugs.