TY - JOUR
T1 - An approach for serotonin depletion in pigs: effects on serotonin receptor binding
AU - Ettrup, Anders
AU - Kornum, Birgitte R
AU - Weikop, Pia
AU - Knudsen, Gitte M
N1 - Copyright © 2010 Wiley-Liss, Inc.
PY - 2011/2
Y1 - 2011/2
N2 - Depletion of central serotonin (5-HT) levels and dysfunction in serotonergic transmission are implicated in a variety of human CNS disorders. The mechanisms behind these serotonergic deficits have been widely studied using rodent models, but only to a limited extent in larger animal models. The pig is increasingly used as an experimental animal model especially in neuroscience research. Here, we present an approach for serotonin depletion in the pig brain. Central serotonin depletion in Danish Landrace pigs was achieved following 4 days treatment with para-chlorophenylalanine (pCPA). On day 5, tissue concentrations of 5-HT in seven distinct brain structures from one hemisphere: frontal and occipital cortex, striatum, hippocampus, cerebellum, rostral, and caudal brain stem, were determined. The other hemisphere was processed for receptor autoradiography. Treatments with 50 mg/kg and 100 mg/kg pCPA caused average decreases in 5-HT concentrations of 61% ± 14% and 66% ± 16%, respectively, and a substantial loss of 5-HT immunostaining was seen throughout the brain. The serotonin depletion significantly increased 5-HT4 receptor binding in nucleus accumbens, but did not alter 5-HT1A and 5-HT2A receptor or serotonin transporter binding in any brain region. In conclusion, 4 days treatment with pCPA effectively reduces 5-HT levels in the pig brain. Further, whereas several 5-HT markers did not change after the pCPA treatment, 5-HT4 receptors were consistently upregulated, indicating a greater susceptibility of this receptor to altered 5-HT levels. This porcine model of serotonin depletion will be useful in future studies of cerebral serotonergic dysfunction. Synapse 2011. © 2010 Wiley-Liss, Inc.
AB - Depletion of central serotonin (5-HT) levels and dysfunction in serotonergic transmission are implicated in a variety of human CNS disorders. The mechanisms behind these serotonergic deficits have been widely studied using rodent models, but only to a limited extent in larger animal models. The pig is increasingly used as an experimental animal model especially in neuroscience research. Here, we present an approach for serotonin depletion in the pig brain. Central serotonin depletion in Danish Landrace pigs was achieved following 4 days treatment with para-chlorophenylalanine (pCPA). On day 5, tissue concentrations of 5-HT in seven distinct brain structures from one hemisphere: frontal and occipital cortex, striatum, hippocampus, cerebellum, rostral, and caudal brain stem, were determined. The other hemisphere was processed for receptor autoradiography. Treatments with 50 mg/kg and 100 mg/kg pCPA caused average decreases in 5-HT concentrations of 61% ± 14% and 66% ± 16%, respectively, and a substantial loss of 5-HT immunostaining was seen throughout the brain. The serotonin depletion significantly increased 5-HT4 receptor binding in nucleus accumbens, but did not alter 5-HT1A and 5-HT2A receptor or serotonin transporter binding in any brain region. In conclusion, 4 days treatment with pCPA effectively reduces 5-HT levels in the pig brain. Further, whereas several 5-HT markers did not change after the pCPA treatment, 5-HT4 receptors were consistently upregulated, indicating a greater susceptibility of this receptor to altered 5-HT levels. This porcine model of serotonin depletion will be useful in future studies of cerebral serotonergic dysfunction. Synapse 2011. © 2010 Wiley-Liss, Inc.
U2 - 10.1002/syn.20827
DO - 10.1002/syn.20827
M3 - Journal article
SN - 0887-4476
VL - 65
SP - 136
EP - 145
JO - Synapse
JF - Synapse
IS - 2
ER -