Stanford, SC;
(2014)
Psychostimulants, antidepressants and neurokinin-1 receptor antagonists ('motor disinhibitors') have overlapping, but distinct, effects on monoamine transmission: The involvement of L-type Ca(2+) channels and implications for the treatment of ADHD.
Neuropharmacology
, 87
pp. 9-18.
10.1016/j.neuropharm.2014.03.021.
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Abstract
Both psychostimulants and antidepressants target monoamine transporters and, as a consequence, augment monoamine transmission. These two groups of drugs also increase motor activity in preclinical behavioural screens for antidepressants. Substance P-preferring receptor (NK1R) antagonists similarly increase both motor activity in these tests and monoamine transmission in the brain. In this article, the neurochemical and behavioural responses to these three groups of drugs are compared. It becomes evident that NK1R antagonists represent a distinct class of compounds ('motor disinhibitors') that differ substantially from both psychostimulants and antidepressants, especially during states of heightened arousal or stress. Also, all three groups of drugs influence the activation of voltage-gated Ca(v)1.2 and Ca(v)1.3 L-type channels (LTCCs) in the brain, albeit in different ways. This article discusses evidence that points to disruption of these functional interactions between NK1R and LTCCs as a contributing factor in the cognitive and behavioural abnormalities that are prominent features of Attention Deficit Hyperactivity Disorder (ADHD). Arising from this is the interesting possibility that the hyperactivity and impulsivity (as in ADHD) and psychomotor retardation (as in depression), reflect opposite poles of a behavioural continuum. A better understanding of this pharmacological network could help explain why psychostimulants augment motor behaviour during stress (e.g., in preclinical screens for antidepressants) and yet reduce locomotor activity and impulsivity in ADHD. This article is part of a Special Issue entitled 'CNS Stimulants'.
| Type: | Article |
|---|---|
| Title: | Psychostimulants, antidepressants and neurokinin-1 receptor antagonists ('motor disinhibitors') have overlapping, but distinct, effects on monoamine transmission: The involvement of L-type Ca(2+) channels and implications for the treatment of ADHD |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1016/j.neuropharm.2014.03.021 |
| Publisher version: | http://dx.doi.org/10.1016/j.neuropharm.2014.03.021 |
| Language: | English |
| Additional information: | Copyright © 2014 The Author. Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/3.0/). |
| Keywords: | Attention Deficit Hyperactivity Disorder (ADHD) antidepressant, L-type calcium channel (LTCC), Monoamine transmission, Neurokinin receptor (NK1R) antagonist, Nifedipine, Psychostimulant |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences |
| URI: | https://discovery.ucl.ac.uk/id/eprint/1427294 |
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