title: The effects of chronic haloperidol administration on GABA-immunoreactive axon terminals in rat medial prefrontal cortex.
abstract: Several reports have suggested that chronic haloperidol (HAL) treatment induces ultrastructural changes in synapses of substantia nigra, corpus striatum, and medial prefrontal cortex (mPFC) of rat brain. The effects of HAL on specific cortical transmitter systems, however, are not well characterized. Recent studies have indicated that there may be a loss of gamma-aminobutyric acid (GABA)ergic cells in anterior cingulate cortex of schizophrenic subjects and this hypothesis has prompted interest in the question of whether dopamine receptor antagonists, such as HAL, may influence the activity of this transmitter system. This current report describes a quantitative light microscopic analysis of GABA-immunolabeled axosomatic terminals in mPFC of rats treated with HAL decanoate (0.5 mg/kg/day, i.m.) for a period of 4 months. GABA-containing terminals were visualized with an avidin-biotin immunoperoxidase method for localizing anti-GABA antibodies. Computer-assisted image processing was employed to determine the total number of pixels representing GABA-immunoreaction product in axon terminals that were in direct apposition to pyramidal cell bodies. Drug-treated animals showed a significant increase in the number of pixels representing GABA-immunoreaction product in axosomatic terminals of layers II, III, VI, and VI (93%, 63%, 31%, and 43%, respectively). These data are consistent with the idea that chronic HAL administration may be associated with a significant increase in the amount of GABA present in terminals surrounding pyramidal neurons of rat mPFC. The fact that GABA-containing terminals showed the greatest increase in layer II is not consistent with the known distribution of dopamine afferents to this region which is lowest in superficial laminae. Based on the laminar distribution of non-dopaminergic receptor types that have a high affinity for HAL, the effect of this drug on GABAergic transmission could potentially involve changes that are mediated through mechanisms in which 5-HT2 or sigma opiate receptors play a role.
authors.affiliation: Department of Psychiatry, Harvard Medical School, Boston, Massachusetts 02115.
authors.forename: S L
authors.initials: SL
authors.lastname: Vincent
authors.forename: E
authors.initials: E
authors.lastname: Adamec
authors.forename: I
authors.initials: I
authors.lastname: Sorensen
authors.forename: F M
authors.initials: FM
authors.lastname: Benes
mesh_terms: D000818:Animals; D001369:Axons / Q000378:metabolism*; D006220:Haloperidol / Q000008:administration & dosage* / Q000494:pharmacology; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D008297:Male; D009411:Nerve Endings / Q000378:metabolism*; D017397:Prefrontal Cortex / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D012044:Regression Analysis; D013997:Time Factors; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D005680:gamma-Aminobutyric Acid; D006220:Haloperidol