title: Attenuation of the anxiogenic effects of cocaine by 5-HT1Bautoreceptor stimulation in the bed nucleus of the stria terminalis of rats.
abstract: Cocaine produces significant aversive/anxiogenic actions whose underlying neurobiology remains unclear. A possible substrate contributing to these actions is the serotonergic (5-HT) pathway projecting from the dorsal raphé (DRN) to regions of the extended amygdala, including the bed nucleus of the stria terminalis (BNST) which have been implicated in the production of anxiogenic states.
  
  
  
  The present study examined the contribution of 5-HT signaling within the BNST to the anxiogenic effects of cocaine as measured in a runway model of drug self-administration.
  
  
  
  Male Sprague-Dawley rats were fitted with bilateral infusion cannula aimed at the BNST and then trained to traverse a straight alley once a day for a single 1 mg/kg i.v. cocaine infusion delivered upon goal-box entry on each of 16 consecutive days/trials. Intracranial infusions of CP 94,253 (0, 0.25, 0.5, or 1.0 μg/side) were administered to inhibit local 5-HT release via activation of 5-HT1Bautoreceptors. To confirm receptor specificity, the effects of this treatment were then challenged by co-administration of the selective 5-HT1Bantagonist NAS-181.
  
  
  
  Intra-BNST infusions of the 5-HT1Bautoreceptor agonist attenuated the anxiogenic effects of cocaine as reflected by a decrease in runway approach-avoidance conflict behavior. This effect was reversed by the 5-HT1Bantagonist. Neither start latencies (a measure of the subject's motivation to seek cocaine) nor spontaneous locomotor activity (an index of motoric capacity) were altered by either treatment.
  
  
  
  Inhibition of 5-HT1Bsignaling within the BNST selectively attenuated the anxiogenic effects of cocaine, while leaving unaffected the positive incentive properties of the drug.
authors.affiliation: Behavioral Pharmacology Laboratory, Department of Psychological and Brain Sciences, University of California, Santa Barbara, CA, 93106-9660, USA.
authors.forename: Adam K
authors.initials: AK
authors.lastname: Klein
authors.affiliation: Behavioral Pharmacology Laboratory, Department of Psychological and Brain Sciences, University of California, Santa Barbara, CA, 93106-9660, USA.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Brito
authors.affiliation: Behavioral Pharmacology Laboratory, Department of Psychological and Brain Sciences, University of California, Santa Barbara, CA, 93106-9660, USA.
authors.forename: Sayeh
authors.initials: S
authors.lastname: Akhavan
authors.affiliation: Behavioral Pharmacology Laboratory, Department of Psychological and Brain Sciences, University of California, Santa Barbara, CA, 93106-9660, USA.
authors.forename: Dylan R
authors.initials: DR
authors.lastname: Flanagan
authors.affiliation: Behavioral Pharmacology Laboratory, Department of Psychological and Brain Sciences, University of California, Santa Barbara, CA, 93106-9660, USA.
authors.forename: Nikki
authors.initials: N
authors.lastname: Le
authors.affiliation: Behavioral Pharmacology Laboratory, Department of Psychological and Brain Sciences, University of California, Santa Barbara, CA, 93106-9660, USA.
authors.forename: Tatum
authors.initials: T
authors.lastname: Ohana
authors.affiliation: Behavioral Pharmacology Laboratory, Department of Psychological and Brain Sciences, University of California, Santa Barbara, CA, 93106-9660, USA.
authors.forename: Anand S
authors.initials: AS
authors.lastname: Patil
authors.affiliation: Behavioral Pharmacology Laboratory, Department of Psychological and Brain Sciences, University of California, Santa Barbara, CA, 93106-9660, USA.
authors.forename: Erin M
authors.initials: EM
authors.lastname: Purvis
authors.affiliation: Behavioral Pharmacology Laboratory, Department of Psychological and Brain Sciences, University of California, Santa Barbara, CA, 93106-9660, USA.
authors.forename: Carl
authors.initials: C
authors.lastname: Provenzano
authors.affiliation: Behavioral Pharmacology Laboratory, Department of Psychological and Brain Sciences, University of California, Santa Barbara, CA, 93106-9660, USA.
authors.forename: Alex
authors.initials: A
authors.lastname: Wei
authors.affiliation: Behavioral Pharmacology Laboratory, Department of Psychological and Brain Sciences, University of California, Santa Barbara, CA, 93106-9660, USA.
authors.forename: Lucy
authors.initials: L
authors.lastname: Zhou
authors.affiliation: Behavioral Pharmacology Laboratory, Department of Psychological and Brain Sciences, University of California, Santa Barbara, CA, 93106-9660, USA. Aaron.ettenberg@psych.ucsb.edu.
authors.forename: Aaron
authors.initials: A
authors.lastname: Ettenberg
mesh_terms: D000818:Animals; D001007:Anxiety; D017660:Autoreceptors / Q000187:drug effects*; D001578:Benzopyrans / Q000494:pharmacology; D003042:Cocaine / Q000008:administration & dosage* / Q000494:pharmacology; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage* / Q000494:pharmacology; D058999:Drug-Seeking Behavior / Q000187:drug effects; D008124:Locomotion / Q000187:drug effects; D008297:Male; D009025:Morpholines / Q000494:pharmacology; D009042:Motivation; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D044302:Receptor, Serotonin, 5-HT1B / Q000187:drug effects*; D012646:Self Administration; D012686:Septal Nuclei / Q000187:drug effects*; D058829:Serotonin 5-HT1 Receptor Antagonists / Q000494:pharmacology
chemical_list: C112429:2-(((3-(morpholinylmethyl)-2H-chromen-8-yl)oxy)methyl)morpholine; D017660:Autoreceptors; D001578:Benzopyrans; C097067:CP 94253; D018765:Dopamine Uptake Inhibitors; D009025:Morpholines; D011725:Pyridines; D044302:Receptor, Serotonin, 5-HT1B; D058829:Serotonin 5-HT1 Receptor Antagonists; D003042:Cocaine
keywords: 5-HT; Anxiety; Cocaine; Drug abuse; Drug aversion; Drug reward; Extended amygdala; Operant runway; Self-administration; Serotonin