Selective dopamine D4 receptor agonist (A-412997) improves cognitive performance and stimulates motor activity without influencing reward-related behaviour in rat
| Autor: | Charlie Reavill, Kerry A. Waters, Laurent P. Lacroix, Enzo Valerio, Sharlene Bull, Abbe Martyn, Declan N.C. Jones, Marie L. Woolley, Simon T. Bate, Lee A. Dawson, Daniel M. Hutcheson |
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| Rok vydání: | 2008 |
| Předmět: |
Agonist
Male Side effect medicine.drug_class Pyridines Dopamine Microdialysis Motor Activity Rats Sprague-Dawley Cognition Reward Acetamides Medicine Attention deficit hyperactivity disorder Animals Effects of sleep deprivation on cognitive performance Receptor Dopamine transporter Pharmacology Memory Disorders biology Behavior Animal Dose-Response Relationship Drug business.industry Drug Administration Routes Receptors Dopamine D4 Extracellular Fluid medicine.disease Acetylcholine Rats Psychiatry and Mental health Amphetamine Disease Models Animal Pattern Recognition Visual A-412997 Dopamine Agonists biology.protein Methylphenidate business Neuroscience Photic Stimulation medicine.drug |
| Zdroj: | Behavioural pharmacology. 19(8) |
| ISSN: | 1473-5849 |
| Popis: | Current therapies for attention deficit hyperactivity disorder comprise psychostimulants, which block the dopamine transporter and/or stimulate the release of dopamine, leading to a global elevation in extrasynaptic dopamine. These drugs are, however, associated with a series of unwanted side effects such as insomnia, anorexia, headache, stomach problems and potential drug abuse. Recent evidence suggests that the dopamine D4 receptor may represent a selective dopamine target that could mediate cognitive as well as striatal motor processes. In this study we compare the effects of a selective D4 receptor agonist, A-412997, with methylphenidate or amphetamine in preclinical models of efficacy versus abuse liability. Both methylphenidate and A-412997 improved a temporally induced deficit in the rat novel object recognition task at doses 10-fold lower than those stimulating activity. In both cases, procognitive doses were associated with elevated extracellular levels of dopamine and acetylcholine in the medial prefrontal cortex. In contrast to amphetamine, A-412997 did not mediate reward-related behaviour in the conditioned place preference paradigm, a preclinical rodent test used to assess potential abuse liability. Collectively, these data suggest that selective activation of the D4 receptor may represent a target for the treatment of attention deficit hyperactivity disorder without the potential drug abuse liability associated with current psychostimulant therapies. |
| Databáze: | OpenAIRE |
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