title: Subchronic administration of atomoxetine causes an enduring reduction in context-induced relapse to cocaine seeking without affecting impulsive decision making.
abstract: Previous work has established a robust relationship between impulsivity and addiction, and revealed that impulsive decision making predisposes the vulnerability to cocaine-seeking behavior in rats. An important next step is to assess whether elevated relapse vulnerability can be treated via the reduction of impulsive decision making. Therefore, this study explored whether subchronic atomoxetine treatment can reduce relapse vulnerability by reducing impulsive decision making. Rats were trained in the delayed reward task and were subjected to 3 weeks of cocaine self-administration. Following drug self-administration, animals were divided to different experimental groups and received the noradrenaline transporter inhibitor and attention-deficit/hyperactivity disorder drug atomoxetine or vehicle subchronically for 20 days. On days 1 and 10 after treatment cessation, a context-induced reinstatement test was performed. Throughout the entire experiment, changes in impulsive decision making were continuously monitored. Subchronic treatment with atomoxetine reduced context-induced reinstatement both 1 and 10 days after treatment cessation, only in animals receiving no extinction training. Interestingly, neither subchronic nor acute atomoxetine treatments affected impulsive decision making. Our data indicate that the enduring reduction in relapse sensitivity by atomoxetine occurred independent of a reduction in impulsive decision making. Nonetheless, repeated atomoxetine administration seems a promising pharmacotherapeutical strategy to prevent relapse to cocaine seeking in abstinent drug-dependent subjects.
authors: Department of Anatomy and Neurosciences, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands.
authors: Nienke
authors: N
authors: Broos
authors: Department of Anatomy and Neurosciences, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands.
authors: Rhianne
authors: R
authors: Loonstra
authors: Department of Anatomy and Neurosciences, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands.
authors: Yvar
authors: Y
authors: van Mourik
authors: Department of Anatomy and Neurosciences, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands.
authors: Dustin
authors: D
authors: Schetters
authors: Department of Anatomy and Neurosciences, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands.
authors: Anton N M
authors: AN
authors: Schoffelmeer
authors: Department of Anatomy and Neurosciences, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands.
authors: Tommy
authors: T
authors: Pattij
authors: Department of Anatomy and Neurosciences, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands.
authors: Taco J
authors: TJ
authors: De Vries
mesh_terms: D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology*; D000818:Animals; D000069445:Atomoxetine Hydrochloride / Q000494:pharmacology*; D003042:Cocaine / Q000008:administration & dosage; D019970:Cocaine-Related Disorders / Q000517:prevention & control*; D003216:Conditioning, Operant; D065786:Delay Discounting / Q000187:drug effects; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage; D058999:Drug-Seeking Behavior / Q000187:drug effects; D005108:Extinction, Psychological / Q000187:drug effects; D007175:Impulsive Behavior / Q000187:drug effects; D008297:Male; D011897:Random Allocation; D017208:Rats, Wistar; D012008:Recurrence; D012055:Reinforcement Schedule; D012646:Self Administration
chemical_list: D018759:Adrenergic Uptake Inhibitors; D018765:Dopamine Uptake Inhibitors; D000069445:Atomoxetine Hydrochloride; D003042:Cocaine
keywords: Addiction; atomoxetine; cocaine; decision making; impulsivity; reinstatement