Clorgyline treatment elevates cortical serotonin and temporarily disrupts the vibrissae-related pattern in rat somatosensory cortex.

Abstract

Manipulation of cortical serotonin (5-HT) levels in perinatal rodents produces significant alterations in the development of the layer IV cortical representation of the mystacial vibrissae. Monoamine oxidase A (MAO(A)) knockout mice have highly elevated cortical 5-HT and completely lack barrels in somatosensory cortex (S-I). The present study was undertaken to determine whether the effects on thalamocortical development seen in MAO(A) knockout mice can be replicated in perinatal rats treated with an MAO(A) inhibitor and, second, to determine whether these effects persist with continued treatment or after discontinuation of the drug. Littermates were injected with either clorgyline (5 mg/kg) or sterile saline five times daily. Clorgyline administration from birth to postnatal day (P) 6, 8, or 10 produced increases of 1,589.4 +/- 53.3%, 1660.2 +/- 43.1% and 1,700.5 +/- 84.5 %, respectively, in cortical 5-HT as compared with controls. Serotonin immunocytochemistry, 1,1;-dioctadecyl-3,3,3", 3;-tetramethylindocarbocyanine perchlorate (DiI) labeling of thalamocortical afferents and Nissl and cytochrome oxidase staining of layer IV cellular aggregates demonstrated that clorgyline treatment from P0 to P6 produced a complete absence of any segmentation of vibrissae-related patches in S-I. However, continued treatment until P8 or P10 did not prevent the appearance of these patches. Animals treated with clorgyline from birth to P6 and killed on P8 or P10 had increases of 546.8 +/- 33.2% and 268.8 +/- 6.3% in cortical 5-HT and they had qualitatively normal vibrissae-related patterns in S-I. These results indicate that clorgyline treatment produces a transient disruption of vibrissae-related patterns, despite the continued presence of elevated cortical 5-HT.