Molecular Pharmacology, Vol 16, 886-899, Copyright © 1979 by the American Society for Pharmacology and Experimental Therapeutics

Regional High-Affinity [³H]Choline Accumulation in Cat Forebrain: Selective Increase in the Caudate-Putamen After Corticosteroid Pretreatment

¹ Department of Pharmacology, Yale University School of Medicine, New Haven, Connecticut, 06510 and Department of Pharmacology, Cornell University Medical College, New York, New York 10021

The effect of acute and chronic gluco- and mineralocorticoid treatment on high-affinity [³H]choline accumulation (HACA) was investigated in cat brain synaptosomes. HACA in forebrain synaptosomes was found to be Na⁺- and energy-dependent, hemicholinium-3 sensitive (K_i 2.5 nM), and of high affinity (apparent K_T = 0.43-0.63 µM). The rank order of regional HACA at 0.04 µM choline (4 min at 37°) was: caudate-putamen-anterior perforated space > hippocampus > prefrontal neocortex. HACA in caudate-putamen synaptosomes was significantly elevated 37-75% after daily treatment for one week with either triamcinolone diacetate (8 mg/kg), hydrocortisone acetate (4 or 32 mg/kg), or deoxycorticosterone acetate (32 mg/kg), but not with l1-epicortisol (8 mg/kg), a biologically inert epimer of hydrocortisone. Treatment-induced increases in caudate-putamen HACA were attributable to an increase (45-53%) in the maximal transport velocity (V_max) and not in the apparent transport constant (K_T). Significant increases in HACA were not seen in the hippocampus-fornix, anterior perforated space, or prefrontal cortex. Acute treatment of cats with a single intravenous dose of methylprednisolone sodium succinate (90 mg/kg) produced 75-84% increases in HACA in caudate-putamen and hippocampus-fornix three hours after treatment. At 24 hours HACA was increased (70 & 76%) in the caudate-putamen and anterior perforated space. Increases in HACA found in the caudate-putamen after in vivo treatment could not be produced by in vitro addition of steroids or alterations of the Na⁺/K⁺ environment. We conclude that the velocity of high-affinity transport of choline into cat brain synaptosomes is strongly and selectively increased in the caudate-putamen after acute or chronic gluco- or mineralocorticoid treatment. The possible explanations for this selectivity are discussed with reference to the neurochemistry and neuropharmacology of the caudate-putamen.

Note:
ACKNOWLEDGMENTS We would like to thank Dr. Les Choi for help in setting up the choline uptake assay and Drs. A. Rifkind and C. Inturrisi for advice. Dr. E. Hall and Ms. M. Bernabe provided excellent technical assistance.