title: Chronic blockade or constitutive deletion of the serotonin transporter reduces operant responding for food reward.
abstract: The therapeutic effects of chronic selective serotonin reuptake inhibitors (SSRIs) are well documented, yet the elementary behavioral processes that are affected by such treatment have not been fully investigated. We report here the effects of chronic fluoxetine treatment and genetic deletion of the serotonin transporter (SERT) on food reinforced behavior in three paradigms: the progressive ratio operant task, the concurrent choice operant task, and the Pavlovian-to-Instrumental transfer task. We consistently find that chronic pharmacological blockade or genetic deletion of SERT result in similar behavioral consequences: reduced operant responding for natural reward. This is in line with previous studies reporting declines in operant responding for drugs and intracranial self-stimulation with fluoxetine treatment, suggesting that the effect of SERT blockade can be generalized to different reward types. Detailed analyses of behavioral parameters indicate that this reduction in operant responding affect both goal-directed and non-goal-directed behaviors without affecting the Pavlovian cue-triggered excessive operant responding. In addition, both pharmacological and genetic manipulations reduce locomotor activity in the open field novel environment. Our data contrast with the effect of dopamine in increasing operant responding for natural reward specifically in goal-directed behaviors and in increasing Pavlovian cue-triggered excessive operant responding. Serotonin and dopamine have been proposed to serve opposing functions in motivational processes. Our data suggest that their interactions do not result in simple opponency. The fact that pharmacological blockade and genetic deletion of SERT have similar behavioral consequences reinforces the utility of the SERT null mice for investigation of the mechanisms underlying chronic SSRIs treatment.
authors.affiliation: Department of Neurobiology, Pharmacology and Physiology, The University of Chicago, Chicago, IL 60637, USA.
authors.forename: Amy Cecilia
authors.initials: AC
authors.lastname: Sanders
authors.forename: Ali J
authors.initials: AJ
authors.lastname: Hussain
authors.forename: René
authors.initials: R
authors.lastname: Hen
authors.forename: Xiaoxi
authors.initials: X
authors.lastname: Zhuang
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal; D002755:Choice Behavior / Q000187:drug effects; D003214:Conditioning, Classical / Q000187:drug effects / Q000502:physiology; D003216:Conditioning, Operant / Q000187:drug effects / Q000502:physiology*; D004435:Eating / Q000187:drug effects; D005473:Fluoxetine / Q000008:administration & dosage; D005518:Food Preferences / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D012201:Reward; D012646:Self Administration; D050486:Serotonin Plasma Membrane Transport Proteins / Q000172:deficiency / Q000378:metabolism*; D017367:Selective Serotonin Reuptake Inhibitors / Q000008:administration & dosage; D013997:Time Factors
chemical_list: D005473:Fluoxetine; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors