title: Modification of the behavioral effects of morphine in rats by serotonin 5-HT₁A and 5-HT₂A receptor agonists: antinociception, drug discrimination, and locomotor activity.
abstract: BACKGROUND
  Indirect-acting serotonin (5-HT) receptor agonists can enhance the antinociceptive effects of morphine; however, the specific 5-HT receptor subtype(s) mediating this enhancement is not established.
  
  
  OBJECTIVE
  This study examined interactions between morphine and both 5-HT(1A) and 5-HT(2A) receptor agonists in rats using measures of antinociception (radiant heat tail flick and warm water tail withdrawal), drug discrimination (3.2 mg/kg morphine versus saline), and locomotion.
  
  
  METHODS
  Male Sprague-Dawley rats (n = 7-8 per group) were used to examine the effects of morphine alone and in combination with DOM (5-HT(2A) agonist) and 8-OH-DPAT (5-HT(1A) agonist).
  
  
  RESULTS
  DOM did not modify antinociceptive or discriminative stimulus effects while modestly attenuating locomotor-stimulating effects of morphine; the effect of DOM (0.32 mg/kg) on morphine-induced locomotion was prevented by the 5-HT(2A) receptor-selective antagonist MDL 100907. In contrast, 8-OH-DPAT (0.032-0.32 mg/kg) fully attenuated the antinociceptive effects (both procedures), did not modify the discriminative stimulus effects, and enhanced (0.32 mg/kg) the locomotor-stimulating effects of morphine. These effects of 8-OH-DPAT were prevented by the 5-HT(1A) receptor-selective antagonist WAY100635.
  
  
  CONCLUSIONS
  Agonists acting at 5-HT(1A) or 5-HT(2A) receptors do not modify all effects of mu opioid receptor agonists in a similar manner. Moreover, interactions between 5-HT and opioid receptor agonists vary significantly between rats and nonhuman primates, underscoring the value of comparing drug interactions across a broad range of conditions and in multiple species.
authors.affiliation: Department of Pharmacology, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229-3900, USA.
authors.forename: Jun-Xu
authors.initials: JX
authors.lastname: Li
authors.forename: Aparna P
authors.initials: AP
authors.lastname: Shah
authors.forename: Sunny K
authors.initials: SK
authors.lastname: Patel
authors.forename: Kenner C
authors.initials: KC
authors.lastname: Rice
authors.forename: Charles P
authors.initials: CP
authors.lastname: France
mesh_terms: D000700:Analgesics / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D004192:Discrimination, Psychological / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D008297:Male; D009020:Morphine / Q000494:pharmacology* / Q000627:therapeutic use; D009043:Motor Activity / Q000187:drug effects* / Q000502:physiology; D010146:Pain / Q000188:drug therapy / Q000523:psychology; D010147:Pain Measurement / Q000187:drug effects / Q000379:methods; D051381:Rats; D017207:Rats, Sprague-Dawley; D044282:Receptor, Serotonin, 5-HT1A / Q000502:physiology*; D044402:Receptor, Serotonin, 5-HT2A / Q000502:physiology*; D058825:Serotonin 5-HT1 Receptor Agonists / Q000494:pharmacology* / Q000627:therapeutic use; D058826:Serotonin 5-HT2 Receptor Agonists / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D000700:Analgesics; D044402:Receptor, Serotonin, 5-HT2A; D058825:Serotonin 5-HT1 Receptor Agonists; D058826:Serotonin 5-HT2 Receptor Agonists; D044282:Receptor, Serotonin, 5-HT1A; D009020:Morphine