title: Axo-axonic structures in the medial prefrontal cortex of the rat: reduction by prenatal exposure to cocaine.
abstract: The cognitive deficits associated with prenatal exposure to cocaine have been hypothesized to be the results of changes in the anatomy and function of the frontal cortex. In this study, pregnant dams were treated with cocaine (3 mg/kg i.v. twice a day) and the resulting adolescent (postnatal day, approximately 45) male offspring were killed for immunocytochemical determination of the total linear measure, number, location, and lengths of inhibitory GABA transporter-1 immunoreactive axo-axonic structures commonly called "candles" or "cartridges" in the medial prefrontal cortex. These inhibitory structures are the axon terminals of GABAergic cells that impinge on the initial axon segments of excitatory pyramidal neurons. We report that prenatal cocaine exposure decreased the number of these inhibitory candles. The greatest reduction of candles was observed in the ventral prelimbic cortex. Additionally, there was a subtle difference in the pattern of distribution of candles, namely the depth of the initial candle in the ventral portions of the prefrontal cortex was greater in rats exposed to prenatal cocaine. However, there was no overt change in the number of cells that were immunoreactive for the calcium-binding protein parvalbumin, an indicator of a subset of GABAergic interneurons that includes axo-axonic chandelier cells. We conclude that exposure to cocaine in utero disrupts the development of the axo-axonic cells in the prefrontal cortex and this disruption could contribute to the cognitive deficits reported with prenatal cocaine exposure.
authors.affiliation: Neuropsychopharmacology Research Unit, Departments of Pharmacology and Psychiatry, Yale University School of Medicine, New Haven, Connecticut 06520-8066, USA. bret.morrow@yale.edu
authors.forename: Bret A
authors.initials: BA
authors.lastname: Morrow
authors.forename: John D
authors.initials: JD
authors.lastname: Elsworth
authors.forename: Robert H
authors.initials: RH
authors.lastname: Roth
mesh_terms: D000818:Animals; D001369:Axons / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure*; D002352:Carrier Proteins / Q000096:biosynthesis; D002452:Cell Count; D003042:Cocaine / Q000494:pharmacology*; D003072:Cognition Disorders / Q000209:etiology; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology; D004334:Drug Administration Schedule; D005260:Female; D050485:GABA Plasma Membrane Transport Proteins; D008297:Male; D008565:Membrane Proteins / Q000096:biosynthesis; D026901:Membrane Transport Proteins; D009433:Neural Inhibition; D027361:Organic Anion Transporters; D010320:Parvalbumins / Q000096:biosynthesis; D017397:Prefrontal Cortex / Q000187:drug effects* / Q000648:ultrastructure; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D017729:Presynaptic Terminals / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D017966:Pyramidal Cells / Q000187:drug effects / Q000648:ultrastructure; D051381:Rats; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; D018765:Dopamine Uptake Inhibitors; D050485:GABA Plasma Membrane Transport Proteins; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D027361:Organic Anion Transporters; D010320:Parvalbumins; D005680:gamma-Aminobutyric Acid; D003042:Cocaine