title: Effects of repeated morphine on ultrasonic vocalizations in adult rats: increased 50-kHz call rate and altered subtype profile.
abstract: Adult rat 50-kHz vocalizations have been proposed to indicate a positive affective state, putatively revealed by a predominance of trill calls over flat calls. However, short-term exposure to non-sedative doses of the euphorigen morphine suppresses calling, with no discernible shift in trill or flat call prevalence.
  
  
  
  This study aimed to determine whether morphine acutely increases 50-kHz call rates or alters the relative prevalence of trill or flat calls, after long-term morphine exposure or acute pharmacological pretreatment.
  
  
  
  Experiment 1 comprised 10 once-daily tests, alternating between saline and morphine, 1 mg/kg SC, followed by dose-response testing (0, 0.3, 1, and 3 mg/kg). Experiment 2 was similar but included additional testing with morphine in combination with the antinausea drug ondansetron or the peripheral opioid antagonist methylnaltrexone. In experiment 3, morphine was again combined with ondansetron or methylnaltrexone but in rats that were initially drug naïve.
  
  
  
  In animals that were initially drug naïve, morphine tended to suppress calling and did not alter the 50-kHz call subtype profile. In morphine-experienced rats, morphine acutely increased the 50-kHz call rate and promoted trills over flat calls; short calls were also inhibited. Neither ondansetron nor methylnaltrexone detectably altered any effect of morphine on calling, nor did these two drugs affect 50-kHz calling when given alone.
  
  
  
  With chronic exposure, morphine acutely enhances 50-kHz calling and differentially promotes trill calls, mainly at the expense of flat calls. These effects appear consistent with a positive affect interpretation of 50-kHz vocalizations.
authors.affiliation: Department of Pharmacology and Therapeutics, McGill University, McIntyre Medical Building Rm. 1320, 3655 Promenade Sir William Osler Montreal, Quebec, H3G 1Y6, Canada.
authors.forename: Laura M
authors.initials: LM
authors.lastname: Best
authors.affiliation: Department of Pharmacology and Therapeutics, McGill University, McIntyre Medical Building Rm. 1320, 3655 Promenade Sir William Osler Montreal, Quebec, H3G 1Y6, Canada.
authors.forename: Leah L
authors.initials: LL
authors.lastname: Zhao
authors.affiliation: Department of Pharmacology and Therapeutics, McGill University, McIntyre Medical Building Rm. 1320, 3655 Promenade Sir William Osler Montreal, Quebec, H3G 1Y6, Canada.
authors.forename: Tina
authors.initials: T
authors.lastname: Scardochio
authors.affiliation: Department of Pharmacology and Therapeutics, McGill University, McIntyre Medical Building Rm. 1320, 3655 Promenade Sir William Osler Montreal, Quebec, H3G 1Y6, Canada. paul.clarke@mcgill.ca.
authors.forename: Paul B S
authors.initials: PB
authors.lastname: Clarke
mesh_terms: D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D051381:Rats; D020318:Rats, Long-Evans; D014828:Vocalization, Animal / Q000187:drug effects*
chemical_list: D000701:Analgesics, Opioid; D009020:Morphine
keywords: Aversion; Methylnaltrexone; Morphine; Ondansetron; Opioid; Reward; Ultrasonic vocalization