Antagonism of L-type Ca(v) channels with nifedipine differentially affects performance of wildtype and NK1R-/- mice in the 5-Choice Serial Reaction-Time Task

Dudley, Julia A, Weir, Ruth K, Yan, Ting C, Grabowska, Ewelina M, Grimmé, Ashley J, Amini, Susana, Stephens, David N, Hunt, Stephen P and Stanford, S Clare (2013) Antagonism of L-type Ca(v) channels with nifedipine differentially affects performance of wildtype and NK1R-/- mice in the 5-Choice Serial Reaction-Time Task. Neuropharmacology, 64 (1). pp. 329-336. ISSN 1873-7064

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Abstract

Mice with functional ablation of the substance P-preferring receptor gene ('Nk1r' in mice ('NK1R-/-'), 'TACR1' in humans) display deficits in cognitive performance that resemble those seen in patients with Attention Deficit Hyperactivity Disorder (ADHD): namely, inattentiveness, impulsivity and perseveration. A recent report suggested that the L-type Ca(v) channel blocker, nifedipine, can ameliorate behavioral abnormalities of this type in humans. In light of evidence that NK1R antagonists modulate the opening of these L-type channels, we investigated whether nifedipine modifies %premature responses (impulsivity), perseveration or %omissions (inattentiveness) in the 5-Choice Serial Reaction-Time Task (5-CSRTT) and whether the response differs in NK1R-/- and wildtype mice. %Premature responses and perseveration were reduced in both genotypes, although wildtype mice were more sensitive to the effects of nifedipine than NK1R-/- mice. By contrast, nifedipine greatly increased %omissions but, again, was more potent in wildtypes. %Accuracy and locomotor activity were unaffected in either genotype. We infer that behavior of mice in the 5-CSRTT depends on the regulation of striato-cortical networks by L-type Ca(v) channels and NK1R. We further suggest that disruption of NK1R signaling in patients with ADHD, especially those with polymorphisms of the TACR1 gene, could lead to compensatory changes in the activity of L-type channels that underlie or exacerbate their problems. This article is part of a Special Issue entitled 'Cognitive Enhancers'.

Item Type: Article
Schools and Departments: School of Psychology > Psychology
Subjects: B Philosophy. Psychology. Religion > BF Psychology > BF0176 Psychological tests and testing
B Philosophy. Psychology. Religion > BF Psychology > BF0180 Experimental psychology
B Philosophy. Psychology. Religion > BF Psychology > BF0207 Psychotropic drugs and other substances
B Philosophy. Psychology. Religion > BF Psychology > BF0309 Consciousness. Cognition Including learning, attention, comprehension, memory, imagination, genius, intelligence, thought and thinking, psycholinguistics, mental fatigue
B Philosophy. Psychology. Religion > BF Psychology > BF0511 Affection. Feeling. Emotion
B Philosophy. Psychology. Religion > BF Psychology > BF0699 Genetic psychology
B Philosophy. Psychology. Religion > BF Psychology > BF0712 Developmental psychology Including infant psychology, child psychology, adolescence, adulthood > BF0724 Adolesence. Youth
Depositing User: Dai Stephens
Date Deposited: 28 Feb 2013 11:26
Last Modified: 28 Feb 2013 11:26
URI: http://sro.sussex.ac.uk/id/eprint/43837

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