Brain potentials and attention after acute and subchronic intranasal administration ofACTH 4-10 and desacetyl-alpha-MSH in humans.
Neuropeptides related to adrenocorticotropin (ACTH) are potent regulators of neurobehavioral functions. In humans, ACTH and its behaviorally active fragment ACTH 4-10 have been consistently found to diminish event-related brain potential (ERP) signs of focussing attention. This study aimed at (1) evaluating effects of ACTH 4-10 on ERP indicators of attention in healthy controls after intranasal administration of the peptide. This route of administration has been proposed to provide a more direct access to the brain than the intravenous administration of the peptide, (2) comparing acute effects and effects of a subchronic treatment with ACTH 4-10, and (3) comparing effects of ACTH 4-10 with those of desacetyl-alpha-MSH (corresponding to ACTH 1-13 amide) which like ACTH 4-10 binds to subgroups of the melanocortin receptor family. Double-blind placebo-controlled experiments were completed in 54 healthy young subjects. ERPs were recorded while the subject performed an auditory selective attention task. Moreover, a modified Stroop interference test including motivational (food, sex) and nonmotivational words was performed. Acute intranasal administration of ACTH 4-10 (1 mg) reduced the processing negativity (PN) of the ERP over frontal and central cortical areas (p < 0.05) indicating diminished focussing of attention. Moreover, on this condition subjects were more prone to interference on the Stroop task especially with motivational words (p < 0.05). Subchronic administration of ACTH 4-10 (1 mg/day over 6 weeks) did not affect PN and Stroop performance. Acute intranasal administration of desacetyl-alpha-MSH at equimolar doses (1.68 mg) also remained ineffective. However, some measures of Stroop performance appeared to improve after subchronic desacetyl-alpha-MSH treatment. Results confirm an acute decrease in focussing of attention after ACTH 4-10. These effects of intranasal administration are likely to reflect a direct action of the peptide on respective brain functions. Moreover, they were specific to ACTH 4-10 and were not obtained after equimolar doses of desacetyl-alpha-MSH, thus excluding a mediation via the known melanocortin receptors.
Department of Internal Medicine, Clinical Neuroendocrinology, University of Lübeck, Germany. smolnik@kfg.uni-luebeck.de
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D000281:Administration, Intranasal; D000324:Adrenocorticotropic Hormone / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D000328:Adult; D001288:Attention / Q000187:drug effects*; D001794:Blood Pressure / Q000187:drug effects; D001921:Brain / Q000187:drug effects*; D004311:Double-Blind Method; D004569:Electroencephalography / Q000187:drug effects; D005071:Evoked Potentials / Q000187:drug effects; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D008297:Male; D009042:Motivation; D018697:Nootropic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D010446:Peptide Fragments / Q000008:administration & dosage / Q000494:pharmacology*; D000521:alpha-MSH / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology
D018697:Nootropic Agents; D010446:Peptide Fragments; D000521:alpha-MSH; D000324:Adrenocorticotropic Hormone; C011394:ACTH (4-10); D006854:Hydrocortisone