title: Targeting pain-depressed behaviors in preclinical assays of pain and analgesia: drug effects on acetic acid-depressed locomotor activity in ICR mice.
abstract: OBJECTIVE
  Pain depresses expression of many behaviors, and one goal of analgesic treatment is to restore pain-depressed behaviors. Assays that focus on pain-depressed behaviors may contribute to preclinical assessment of candidate analgesics.
  
  
  METHODS
  This study compared effects of the mu opioid receptor agonist morphine (an acknowledged analgesic), the dopamine receptor antagonist haloperidol (a non-analgesic sedative), the adenosine receptor antagonist caffeine (a non-analgesic stimulant) and the neurokinin-1 receptor antagonist CJ 11,974-01 (a candidate analgesic) on acetic acid-induced writhing (a traditional pain-stimulated behavior) and acetic acid-induced suppression of locomotor activity (a pain-depressed behavior) in male ICR mice. Drug effects on non-depressed (baseline) locomotor activity were also examined.
  
  
  RESULTS
  I.P. administration of acetic acid (0.18-1%) was equipotent in stimulating writhing and depressing locomotor activity. Morphine blocked both acid-induced stimulation of writhing and depression of locomotion, although it was 56-fold less potent in the assay of acid-depressed locomotion. Haloperidol and CJ 11,974-01 decreased acid-stimulated writhing, but failed to block acid-induced depression of locomotion. Caffeine had no effect on acid-stimulated writhing or acid-depressed locomotor activity, although it did increase non-depressed locomotion. Thus, morphine was the only drug to block both acid-stimulated writhing and acid-depressed locomotion.
  
  
  CONCLUSIONS
  Complementary assays of pain-stimulated and pain-depressed behaviors may improve the predictive validity of preclinical studies that assess candidate analgesic drugs. The low potency of morphine to block acid-induced depression of locomotion suggests that locomotor activity may be a relatively insensitive measure for studies of pain-depressed behavior.
authors: Department of Psychology, University of New England, Biddeford, ME, 04005, United States. gstevenson@une.edu
authors: Glenn W
authors: GW
authors: Stevenson
authors: Jim
authors: J
authors: Cormier
authors: Hannah
authors: H
authors: Mercer
authors: Chloe
authors: C
authors: Adams
authors: Catherine
authors: C
authors: Dunbar
authors: S Stevens
authors: SS
authors: Negus
authors: Edward J
authors: EJ
authors: Bilsky
mesh_terms: D019342:Acetic Acid / Q000494:pharmacology; D000698:Analgesia / Q000379:methods*; D000700:Analgesics / Q000008:administration & dosage / Q000627:therapeutic use*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001555:Benzene Derivatives / Q000008:administration & dosage / Q000627:therapeutic use; D002110:Caffeine / Q000008:administration & dosage / Q000627:therapeutic use; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D006220:Haloperidol / Q000008:administration & dosage / Q000627:therapeutic use; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009020:Morphine / Q000008:administration & dosage / Q000627:therapeutic use; D009043:Motor Activity / Q000187:drug effects*; D010146:Pain / Q000188:drug therapy* / Q000503:physiopathology; D010147:Pain Measurement
chemical_list: D000700:Analgesics; D001555:Benzene Derivatives; C120871:CJ 11974; D002110:Caffeine; D009020:Morphine; D006220:Haloperidol; D019342:Acetic Acid