title: Serotonin depletion attenuates cocaine-seeking behavior in rats.
abstract: BACKGROUND
  Alterations in serotonin (5-HT) neurotransmission during cocaine withdrawal may be involved in incentive motivation for cocaine.
  
  
  OBJECTIVE
  The present study examined the effects of 5-HT depletion on cocaine- and food-seeking behavior (i.e., non-reinforced operant responding).
  
  
  METHODS
  Separate groups of rats were trained to lever press for cocaine infusions (0.33 mg/kg/0.1 ml, i.v.) or for food pellets (45-mg Noyes food pellets) on a fixed-ratio one schedule of reinforcement during 14 daily 2-h sessions. Half of each group then received treatment with either saline or the tryptophan hydroxylase inhibitor para-chlorophenylalanine (p-CPA; 100 mg/kg, i.p.) on post-training day 5 and day 6. Twenty-four hours after their last treatment, rats were tested for cocaine- or food-seeking behavior by measuring operant responding in the absence of reinforcement until they reached an extinction criterion of no responses for 30 min. Animals were sacrificed 24 h after testing and brain 5-HT levels in various regions were quantified.
  
  
  RESULTS
  In cocaine-trained animals, p-CPA treatment significantly decreased cocaine-seeking behavior and produced a trend toward a decrease in extinction latency relative to saline treatment. In food-trained animals, p-CPA treatment failed to alter any of the behavioral measures during testing, suggesting that p-CPA treatment did not alter the animals' memory or ability to perform an operant response. p-CPA significantly depleted 5-HT by 73-85% in every brain region examined.
  
  
  CONCLUSIONS
  The results suggest that decreasing 5-HT neurotransmission may decrease incentive motivation for cocaine.
authors.affiliation: Department of Psychology, Arizona State University, Box 871104, Tempe, AZ 85287-1104, USA, lytran@imap1.asu.edu
authors.forename: L T
authors.initials: LT
authors.lastname: Tran-Nguyen
authors.forename: D A
authors.initials: DA
authors.lastname: Baker
authors.forename: K A
authors.initials: KA
authors.lastname: Grote
authors.forename: J
authors.initials: J
authors.lastname: Solano
authors.forename: J L
authors.initials: JL
authors.lastname: Neisewander
mesh_terms: D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects; D003042:Cocaine / Q000008:administration & dosage*; D004435:Eating; D005108:Extinction, Psychological; D008297:Male; D009042:Motivation; D009043:Motor Activity / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time; D012646:Self Administration; D012701:Serotonin / Q000032:analysis / Q000502:physiology*
chemical_list: D012701:Serotonin; D003042:Cocaine