title: Provision of cues to signal a withdrawal US prevents the US pre-exposure effect in a diazepam-withdrawal conditioned taste aversion.
abstract: BACKGROUND
  Prior experience of withdrawal from chronic diazepam treatment reduces the aversiveness of withdrawal when precipitated withdrawal is made the US in a conditioned taste aversion (CTA) paradigm. Some accounts of US pre-exposure reducing its effectiveness in CTA postulate that US pre-exposure leads to the formation of associations with the environment, resulting in blocking of taste conditioning, but a test of a blocking explanation failed to provide support for such an account.
  
  
  OBJECTIVE
  The present experiments tested alternative explanations.
  
  
  METHODS
  Male mice (C57BLx129sv derived) made dependent upon diazepam (15 mg/kg per day, SC) were subjected to precipitated withdrawal with IP flumazenil (20 mg/kg) as the unconditioned stimulus (US) in a conditioned taste aversion (CTA) paradigm, in which sucrose was the conditioned stimulus (CS). The conditioning trial took place in either the same or different environment from that in which the mice had received pre-exposure to the withdrawal US.
  
  
  RESULTS
  No evidence was found that a place conditioned to withdrawal was capable of supporting a second-order CTA. A second experiment showed that whether withdrawal supported a CTA depended upon whether the previous experience of withdrawal had been predicted by an environmental stimulus.
  
  
  CONCLUSIONS
  Prior experience of an unpredictable aversive US disrupts the subsequent formation of a CTA to the same US. Since prior experience of withdrawal, if it was predictable by an environmental event, did not prevent withdrawal from being a US in a subsequent CTA experiment, withdrawal retains its aversive nature even following prior experience. An explanation in terms of the nature of US predictability following repeated withdrawal from diazepam is consistent both with the current data and our previous findings.
authors.affiliation: Laboratory of Experimental Psychology, University of Sussex, Falmer, Brighton BN1 9QG, UK.
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Dunworth
authors.forename: David N
authors.initials: DN
authors.lastname: Stephens
mesh_terms: D000818:Animals; D014151:Anti-Anxiety Agents / Q000009:adverse effects*; D001362:Avoidance Learning / Q000187:drug effects / Q000502:physiology; D003213:Conditioning, Psychological / Q000187:drug effects* / Q000502:physiology; D003463:Cues; D003975:Diazepam / Q000009:adverse effects*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D013375:Substance Withdrawal Syndrome / Q000523:psychology*; D013649:Taste / Q000187:drug effects* / Q000502:physiology
chemical_list: D014151:Anti-Anxiety Agents; D003975:Diazepam