title: Blockade of 5-HT2A receptors in the medial prefrontal cortex attenuates reinstatement of cue-elicited cocaine-seeking behavior in rats.
abstract: BACKGROUND
  The action of serotonin (5-HT) at the 5-HT(2A) receptor subtype is thought to be involved in cocaine-seeking behavior that is motivated by exposure to drug-associated cues and drug priming. 5-HT(2A) receptors are densely clustered in the ventromedial prefrontal cortex (vmPFC), an area that plays a role in mediating cocaine-seeking behavior.
  
  
  OBJECTIVE
  This study examined the hypothesis that M100907, a 5-HT(2A) receptor antagonist, infused directly in the vmPFC attenuates cue- and cocaine-primed reinstatement of cocaine-seeking behavior.
  
  
  METHODS
  Rats trained to self-administer cocaine (0.75 mg/kg, i.v.) paired with light and tone cues underwent extinction training during which operant responses produced no consequences. Once behavior extinguished, rats were tested for reinstatement of responding elicited by either response-contingent presentations of the cocaine-paired light/tone cues or by cocaine-priming injections (10 mg/kg, i.p.) within 1 min after pretreatment with microinfusions of M100907 (0.1, 0.3, 1.0, or 1.5 μg/0.2 μl/side) into the vmPFC.
  
  
  RESULTS
  Intra-vmPFC M100907 decreased cue-elicited reinstatement at the two highest doses (1.0 and 1.5 μg) but produced only a slight decrease in cocaine-primed reinstatement that was not dose dependent. The decrease in cue reinstatement was not likely due to impaired ability to respond since intra-vmPFC M100907 infusions had minimal effect on cocaine self-administration and no effect on cue-elicited sucrose-seeking behavior, or spontaneous or cocaine-induced locomotion. M100907 infusions into the adjacent anterior cingulate cortex had no effect on cue reinstatement.
  
  
  CONCLUSIONS
  The results suggest that the blockade of 5-HT(2A) receptors in the vmPFC selectively attenuates the incentive motivational effects of cocaine-paired cues.
authors.affiliation: Department of Psychology, Arizona State University, Tempe, AZ 85287, USA.
authors.forename: Lara A
authors.initials: LA
authors.lastname: Pockros
authors.forename: Nathan S
authors.initials: NS
authors.lastname: Pentkowski
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Swinford
authors.forename: Janet L
authors.initials: JL
authors.lastname: Neisewander
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D003042:Cocaine / Q000008:administration & dosage*; D003216:Conditioning, Operant / Q000187:drug effects; D003463:Cues; D004305:Dose-Response Relationship, Drug; D005464:Fluorobenzenes / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D010880:Piperidines / Q000008:administration & dosage / Q000494:pharmacology*; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D044402:Receptor, Serotonin, 5-HT2A / Q000187:drug effects / Q000378:metabolism*; D012646:Self Administration; D058830:Serotonin 5-HT2 Receptor Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D013395:Sucrose / Q000008:administration & dosage
chemical_list: D005464:Fluorobenzenes; D010880:Piperidines; D044402:Receptor, Serotonin, 5-HT2A; D058830:Serotonin 5-HT2 Receptor Antagonists; D013395:Sucrose; C079049:volinanserin; D003042:Cocaine