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The Journal of Neuroscience, June 15, 2003, 23(12):5227-5234

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Axo-Axonic Structures in the Medial Prefrontal Cortex of the Rat: Reduction by Prenatal Exposure to Cocaine

Bret A. Morrow, John D. Elsworth, and Robert H. Roth

Neuropsychopharmacology Research Unit, Departments of Pharmacology and Psychiatry, Yale University School of Medicine, New Haven, Connecticut 06520-8066

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, 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.

Key words: development; GABA transporter-1; GAT-1; dopamine; cartridge; candle

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Received Apr. 1, 2002; revised Apr. 3, 2003; accepted Apr. 11, 2003.

This article has been cited by other articles:

				H. Lu, B. Lim, and M.-m. Poo Cocaine Exposure In Utero Alters Synaptic Plasticity in the Medial Prefrontal Cortex of Postnatal Rats J. Neurosci., October 7, 2009; 29(40): 12664 - 12674. [Abstract] [Full Text] [PDF]

				J. E. Crandall, H. E. Hackett, S. A. Tobet, B. E. Kosofsky, and P. G. Bhide Cocaine Exposure Decreases GABA Neuron Migration from the Ganglionic Eminence to the Cerebral Cortex in Embryonic Mice Cereb Cortex, June 1, 2004; 14(6): 665 - 675. [Abstract] [Full Text] [PDF]

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