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Effects of repeated morphine on ultrasonic vocalizations in adult rats: increased 50-kHz call rate and altered subtype profile

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Abstract

Rationale

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.

Objectives

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.

Methods

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.

Results

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.

Conclusions

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.

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References

  • Altarifi AA, Negus SS (2011) Some determinants of morphine effects on intracranial self stimulation in rats: dose, pretreatment time, repeated treatment, and rate dependence. Behav Pharmacol 22:663–673. doi:10.1097/FBP.0b013e32834aff54

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Aung HH, Mehendale SR, Xie JT, Moss J, Yuan CS (2004) Methylnaltrexone prevents morphine-induced kaolin intake in the rat. Life Sci 74:2685–2691. doi:10.1016/j.lfs.2003.08.047

    Article  CAS  PubMed  Google Scholar 

  • Babbini M, Davis WM (1972) Time-dose relationships for locomotor activity effects of morphine after acute or repeated treatment. Br J Pharmacol 46:213–224

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bardo MT, Rowlett JK, Harris MJ (1995) Conditioned place preference using opiate and stimulant drugs: a meta-analysis. Neurosci Biobehav Rev 19:39–51

    Article  CAS  PubMed  Google Scholar 

  • Bechara A, Zito KA, van der Kooy D (1987) Peripheral receptors mediate the aversive conditioning effects of morphine in the rat. Pharmacol Biochem Behav 28:219–225

    Article  CAS  PubMed  Google Scholar 

  • Burgdorf J, Knutson B, Panksepp J, Shippenberg TS (2001) Evaluation of rat ultrasonic vocalizations as predictors of the conditioned aversive effects of drugs. Psychopharmacology 155:35–42

    Article  CAS  PubMed  Google Scholar 

  • Burgdorf J, Panksepp J, Moskal JR (2011) Frequency-modulated 50 kHz ultrasonic vocalizations: a tool for uncovering the molecular substrates of positive affect. Neurosci Biobehav Rev 35:1831–1836. doi:10.1016/j.neubiorev.2010.11.011

    Article  PubMed  Google Scholar 

  • Coderre TJ, Fundytus ME, McKenna JE, Dalal S, Melzack R (1993) The formalin test: a validation of the weighted-scores method of behavioural pain rating. Pain 54:43–50

    Article  CAS  PubMed  Google Scholar 

  • Craft RM, Kalivas PW, Stratmann JA (1996) Sex differences in discriminative stimulus effects of morphine in the rat. Behav Pharmacol 7:764–778

    CAS  PubMed  Google Scholar 

  • Gaiardi M, Bartoletti M, Bacchi A, Gubellini C, Costa M, Babbini M (1991) Role of repeated exposure to morphine in determining its affective properties: place and taste conditioning studies in rats. Psychopharmacology 103:183–186

    Article  CAS  PubMed  Google Scholar 

  • Gmerek DE, Cowan A, Woods JH (1986) Independent central and peripheral mediation of morphine-induced inhibition of gastrointestinal transit in rats. J Pharmacol Exp Ther 236:8–13

    CAS  PubMed  Google Scholar 

  • Hamed A, Taracha E, Szyndler J, Krzascik P, Lehner M, Maciejak P, Skorzewska A, Plaznik A (2012) The effects of morphine and morphine conditioned context on 50 kHz ultrasonic vocalisation in rats. Behav Brain Res 229:447–450. doi:10.1016/j.bbr.2012.01.053

    Article  CAS  PubMed  Google Scholar 

  • Haney M, Miczek KA (1994) Ultrasounds emitted by female rats during agonistic interactions: effects of morphine and naltrexone. Psychopharmacology 114:441–448

    Article  CAS  PubMed  Google Scholar 

  • Haney M, Miczek KA (1995) Delta opioid receptors: reflexive, defensive and vocal affective responses in female rats. Psychopharmacology 121:204–212

    Article  CAS  PubMed  Google Scholar 

  • Harris AC, Gewirtz JC (2004) Elevated startle during withdrawal from acute morphine: a model of opiate withdrawal and anxiety. Psychopharmacology 171:140–147. doi:10.1007/s00213-003-1573-0

    Article  CAS  PubMed  Google Scholar 

  • Harris AC, Gewirtz JC (2005) Acute opioid dependence: characterizing the early adaptations underlying drug withdrawal. Psychopharmacology 178:353–366. doi:10.1007/s00213-005-2155-0

    Article  CAS  PubMed  Google Scholar 

  • Higgins GA, Nguyen P, Joharchi N, Sellers EM (1991) Effects of 5-HT3 receptor antagonists on behavioural measures of naloxone-precipitated opioid withdrawal. Psychopharmacology 105:322–328

    Article  CAS  PubMed  Google Scholar 

  • Jasinski DR, Pevnick JS, Griffith JD (1978) Human pharmacology and abuse potential of the analgesic buprenorphine: a potential agent for treating narcotic addiction. Arch Gen Psychiatry 35:501–516

    Article  CAS  PubMed  Google Scholar 

  • Kim C, Cheng R, Corrigall WA, Coen KM (1989) Assay for methylnaltrexone in rat brain regions and serum by high-performance liquid chromatography with coulometric electrochemical detection. Chromatographia 28:359–363

    Article  CAS  Google Scholar 

  • Knutson B, Burgdorf J, Panksepp J (2002) Ultrasonic vocalizations as indices of affective states in rats. Psychol Bull 128:961–977

    Article  PubMed  Google Scholar 

  • Lasagna L, von Felsinger JM, Beecher HK (1955) Drug-induced mood changes in man. I. Observations on healthy subjects, chronically ill patients, and postaddicts. J Am Med Assoc 157:1006–1020

    Article  CAS  PubMed  Google Scholar 

  • Lett BT (1989) Repeated exposures intensify rather than diminish the rewarding effects of amphetamine, morphine, and cocaine. Psychopharmacology 98:357–362.29

    Article  CAS  PubMed  Google Scholar 

  • Ludbrook J (2008) Outlying observations and missing values: how should they be handled? Clin Exp Pharmacol Physiol 35:670–678. doi:10.1111/j.1440-1681.2007.04860.x

    Article  CAS  PubMed  Google Scholar 

  • Martin GM, Bechara A, van der Kooy D (1988) Morphine preexposure attenuates the aversive properties of opiates without preexposure to the aversive properties. Pharmacol Biochem Behav 30:687–692

    Article  CAS  PubMed  Google Scholar 

  • Mucha RF, Herz A (1985) Motivational properties of kappa and mu opioid receptor agonists studied with place and taste preference conditioning. Psychopharmacology 86:274–280

    Article  CAS  PubMed  Google Scholar 

  • Pinelli A, Trivulzio S, Tomasoni L (1997) Effects of ondansetron administration on opioid withdrawal syndrome observed in rats. Eur J Pharmacol 340:111–119

    Article  CAS  PubMed  Google Scholar 

  • Scardochio T, Clarke PBS (2013) Inhibition of 50-kHz ultrasonic vocalizations by dopamine receptor subtype-selective agonists and antagonists in rats. Psychopharmacology 225:853–868. doi:10.1007/s00213-012-2931-6

    Article  Google Scholar 

  • Schwarting RK, Jegan N, Wohr M (2007) Situational factors, conditions and individual variables which can determine ultrasonic vocalizations in male adult Wistar rats. Behav Brain Res 182:208–222. doi:10.1016/j.bbr.2007.01.029

    Article  PubMed  Google Scholar 

  • Simola N, Fenu S, Costa G, Pinna A, Plumitallo A, Morelli M (2012) Pharmacological characterization of 50-kHz ultrasonic vocalizations in rats: comparison of the effects of different psychoactive drugs and relevance in drug-induced reward. Neuropharmacology 63:224–234. doi:10.1016/j.neuropharm.2012.03.013

    Article  CAS  PubMed  Google Scholar 

  • Simola N, Frau L, Plumitallo A, Morelli M (2014) Direct and long-lasting effects elicited by repeated drug administration on 50-kHz ultrasonic vocalizations are regulated differently: implications for the study of the affective properties of drugs of abuse. Int J Neuropsychopharmacol 17:429–441. doi:10.1017/S1461145713001235

    Article  CAS  PubMed  Google Scholar 

  • Simola N, Costa G, Morelli M (2016) Activation of adenosine a receptors suppresses the emission of pro-social and drug-stimulated 50-kHz ultrasonic vocalizations in rats: possible relevance to reward and motivation. Psychopharmacology 233:507–519. doi:10.1007/s00213-015-4130-8

    Article  CAS  PubMed  Google Scholar 

  • Simpson GR, Riley AL (2005) Morphine preexposure facilitates morphine place preference and attenuates morphine taste aversion. Pharmacol Biochem Behav 80:471–479. doi:10.1016/j.pbb.2005.01.003

    Article  CAS  PubMed  Google Scholar 

  • Smith GM, Beecher HK (1962) Subjective effects of heroin and morphine in normal subjects. J Pharmacol Exp Ther 136:47–52

    CAS  PubMed  Google Scholar 

  • Takeda N, Hasegawa S, Morita M, Matsunaga T (1993) Pica in rats is analogous to emesis: an animal model in emesis research. Pharmacol Biochem Behav 45:817–821

    Article  CAS  PubMed  Google Scholar 

  • Vasko MR, Domino EF (1978) Tolerance development to the biphasic effects of morphine on locomotor activity and brain acetylcholine in the rat. J Pharmacol Exp Ther 207:848–858.30

    CAS  PubMed  Google Scholar 

  • Vivian JA, Miczek KA (1993) Morphine attenuates ultrasonic vocalization during agonistic encounters in adult male rats. Psychopharmacology 111:367–375

    Article  CAS  PubMed  Google Scholar 

  • Wintink AJ, Brudzynski SM (2001) The related roles of dopamine and glutamate in the initiation of 50-kHz ultrasonic calls in adult rats. Pharmacol Biochem Behav 70:317–323

    Article  CAS  PubMed  Google Scholar 

  • Wright JM, Gourdon J, Clarke PBS (2010) Identification of multiple call categories within the rich repertoire of adult rat 50-kHz ultrasonic vocalizations: effects of amphetamine and social context. Psychopharmacology 211:1–13. doi:10.1007/s00213-010-1859-y

    Article  CAS  PubMed  Google Scholar 

  • Wright JM, Deng L, Clarke PB (2012a) Failure of rewarding and locomotor stimulant doses of morphine to promote adult rat 50-kHz ultrasonic vocalizations. Psychopharmacology 224:477–487. doi:10.1007/s00213-012-2776-z

    Article  CAS  PubMed  Google Scholar 

  • Wright JM, Dobosiewicz MR, Clarke PB (2012b) Alpha- and beta- adrenergic receptors differentially modulate the emission of spontaneous and amphetamine induced 50-kHz ultrasonic vocalizations in adult rats. Neuropsychopharmacology 37:808–821. doi:10.1038/npp.2011.258

    Article  CAS  PubMed  Google Scholar 

  • Ye JH, Ponnudurai R, Schaefer R (2001) Ondansetron: a selective 5-HT(3) receptor antagonist and its applications in CNS-related disorders. CNS Drug Rev 7:199–213

    Article  CAS  PubMed  Google Scholar 

  • Yuan CS, Foss JF, O’Connor M, Osinski J, Roizen MF, Moss J (1998) Efficacy of orally administered methylnaltrexone in decreasing subjective effects after intravenous morphine. Drug Alcohol Depend 52:161–165

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

This study is supported by a Natural Science and Engineering Research Council of Canada (NSERC) discovery grant (155055, to P.B.S.C.) and an NSERC Undergraduate Student Research Award (to L.Z.). P.B.S.C. is a member of the Center for Studies in Behavioral Neurobiology at Concordia University, Montreal. We thank Prof. Chun-Su Yuan, Pritzker School of Medicine, University of Chicago, for his generous gift of methylnaltrexone bromide. The authors have no financial relationship with the organizations that sponsored this research. All experiments comply with the current laws of Canada.

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Authors and Affiliations

  1. Department of Pharmacology and Therapeutics, McGill University, McIntyre Medical Building Rm. 1320, 3655 Promenade Sir William Osler Montreal, Quebec, H3G 1Y6, Canada

    Laura M. Best, Leah L. Zhao, Tina Scardochio & Paul B.S. Clarke

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  1. Laura M. Best
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  2. Leah L. Zhao
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  3. Tina Scardochio
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  4. Paul B.S. Clarke
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Correspondence to Paul B.S. Clarke.

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Best, L.M., Zhao, L.L., Scardochio, T. et al. Effects of repeated morphine on ultrasonic vocalizations in adult rats: increased 50-kHz call rate and altered subtype profile. Psychopharmacology 234, 155–165 (2017). https://doi.org/10.1007/s00213-016-4449-9

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