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Failure of rewarding and locomotor stimulant doses of morphine to promote adult rat 50-kHz ultrasonic vocalizations

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Abstract

Rationale

Frequency-modulated 50-kHz ultrasonic vocalizations (USVs) are emitted by adult rats in response to psychostimulants and non-pharmacological appetitive stimuli and thus have been proposed to model positive affect.

Objective

The main aim was to determine whether rewarding doses of morphine increase 50-kHz call rate or alter the relative prevalence of the trill call subtype.

Methods

In experiment 1, USVs were recorded from adult male Long–Evans rats after subchronic morphine (1 mg/kg subcutaneous (SC)) administration, acute challenge with morphine (1 and 3 mg/kg SC) or amphetamine (1 mg/kg IP, positive control), and in conjunction with locomotor activity tests with morphine (1 and 3 mg/kg SC). In experiments 2 and 3, the USV altering, rewarding, and locomotor effects of morphine were examined using a conditioned place preference (CPP) procedure.

Results

In experiment 1, morphine (1 mg/kg) initially suppressed calling; rats became tolerant to this effect with repeated exposure. Tested subsequently in singly- and pair-tested rats, morphine markedly decreased USVs but significantly increased locomotor activity. In experiments 2 and 3, morphine produced a significant CPP without increasing either unconditioned or conditioned USV emission. Morphine did not detectably alter the relative prevalence of 50-kHz call subtypes.

Conclusions

Although 50-kHz calls, and the trill call subtype in particular, have been proposed as an animal model of positive mood, not all euphoriant drugs acutely increase the rate of 50-kHz calling or consistently promote trill calls.

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References

  • Ahrens AM, Ma ST, Maier EY, Duvauchelle CL, Schallert T (2009) Repeated intravenous amphetamine exposure: rapid and persistent sensitization of 50-kHz ultrasonic trill calls in rats. Behav Brain Res 197:205–209

    Article  PubMed  CAS  Google Scholar 

  • Angrist B, Sathananthan G, Wilk S, Gershon S (1974) Amphetamine psychosis: behavioral and biochemical aspects. J Psychiatr Res 11:13–23

    Article  PubMed  CAS  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  PubMed  CAS  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  PubMed  CAS  Google Scholar 

  • Bechara A, van der Kooy D (1985) Opposite motivational effects of endogenous opioids in brain and periphery. Nature 314:533–534

    Article  PubMed  CAS  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  PubMed  CAS  Google Scholar 

  • Berridge KC, Robinson TE (2003) Parsing reward. Trends Neurosci 26:507–513

    Article  PubMed  CAS  Google Scholar 

  • Biala G, Kruk M (2007) Amphetamine-induced anxiety-related behavior in animal models. Pharmacol Rep 59:636–644

    PubMed  CAS  Google Scholar 

  • Bird SJ, Kuhar MJ (1977) Iontophoretic application of opiates to the locus coeruleus. Brain Res 122:523–533

    Article  PubMed  CAS  Google Scholar 

  • Brudzynski SM (2007) Ultrasonic calls of rats as indicator variables of negative or positive states: acetylcholine–dopamine interaction and acoustic coding. Behav Brain Res 182:261–273

    Article  PubMed  CAS  Google Scholar 

  • Brudzynski SM (2009) Communication of adult rats by ultrasonic vocalization: biological, sociobiological, and neuroscience approaches. ILAR J 50:43–50

    PubMed  CAS  Google Scholar 

  • Brudzynski SM, Pniak A (2002) Social contacts and production of 50-kHz short ultrasonic calls in adult rats. J Comp Psychol 116:73–82

    Article  PubMed  Google Scholar 

  • Burgdorf J, Moskal JR (2009) Frequency modulated 50 kHz ultrasonic vocalizations reflect a positive emotional state in the rat: neural substrates and therapeutic implications. In: Brudzynski SM (ed) Handbook of mammalian vocalization. Academic, Oxford, pp 209–214

    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 (Berl) 155:35–42

    Article  CAS  Google Scholar 

  • Burgdorf J, Kroes RA, Moskal JR, Pfaus JG, Brudzynski SM, Panksepp J (2008) Ultrasonic vocalizations of rats (Rattus norvegicus) during mating, play, and aggression: behavioral concomitants, relationship to reward, and self-administration of playback. J Comp Psychol 122:357–367

    Article  PubMed  Google Scholar 

  • Burgdorf J, Panksepp J, Moskal JR (2010) Frequency-modulated 50 kHz ultrasonic vocalizations: a tool for uncovering the molecular substrates of positive affect. Neurosci Biobehav Rev 35:1831–1836

    Article  PubMed  Google Scholar 

  • Calcagnetti DJ, Schechter MD (1992) Place conditioning reveals the rewarding aspect of social interaction in juvenile rats. Physiol Behav 51:667–672

    Article  PubMed  CAS  Google Scholar 

  • Ciucci MR, Ma ST, Fox C, Kane JR, Ramig LO, Schallert T (2007) Qualitative changes in ultrasonic vocalization in rats after unilateral dopamine depletion or haloperidol: a preliminary study. Behav Brain Res 182:284–289

    Article  PubMed  CAS  Google Scholar 

  • Covington HEI, Miczek KA (2003) Vocalizations during withdrawal from opiates and cocaine: possible expressions of affective distress. Eur J Pharmacol 467:1–13

    Article  PubMed  CAS  Google Scholar 

  • Dinh HK, Larkin A, Gatlin L, Piepmeier E Jr (1999) Rat ultrasound model for measuring pain resulting from intramuscularly injected antimicrobials. PDA J Pharm Sci Technol 53:40–43

    PubMed  CAS  Google Scholar 

  • Fernandes M, Kluwe S, Coper H (1977) The development of tolerance to morphine in the rat. Psychopharmacology (Berl) 54:197–201

    Article  CAS  Google Scholar 

  • File SE, Hyde JR (1979) A test of anxiety that distinguishes between the actions of benzodiazepines and those of other minor tranquilisers and of stimulants. Pharmacol Biochem Behav 11:65–69

    Article  PubMed  CAS  Google Scholar 

  • Fog R (1970) Behavioural effects in rats of morphine and amphetamine and of a combination of the two drugs. Psychopharmacologia 16:305–312

    Article  PubMed  CAS  Google Scholar 

  • Foltin RW, Fischman MW (1991) Assessment of abuse liability of stimulant drugs in humans: a methodological survey. Drug Alcohol Depend 28:3–48

    Article  PubMed  CAS  Google Scholar 

  • Hamdani S, White NM (2011) Ultrasonic vocalization ratios reflect the influence of motivational state and amygdala lesions on different types of taste avoidance learning. Behav Brain Res 217:88–98

    Article  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

    Article  PubMed  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  • Jasinski DR, Preston KL (1986) Evaluation of mixtures of morphine and d-amphetamine for subjective and physiological effects. Drug Alcohol Depend 17:1–13

    Article  PubMed  CAS  Google Scholar 

  • Kaltwasser MT (1990) Acoustic signaling in the black rat (Rattus rattus). J Comp Psychol 104:227–232

    Article  PubMed  CAS  Google Scholar 

  • Knutson B, Burgdorf J, Panksepp J (1999) High-frequency ultrasonic vocalizations index conditioned pharmacological reward in rats. Physiol Behav 66:639–643

    Article  PubMed  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 

  • Korf J, Bunney BS, Aghajanian GK (1974) Noradrenergic neurons: morphine inhibition of spontaneous activity. Eur J Pharmacol 25:165–169

    Article  PubMed  CAS  Google Scholar 

  • Lett BT (1989) Repeated exposures intensify rather than diminish the rewarding effects of amphetamine, morphine, and cocaine. Psychopharmacology (Berl) 98:357–362

    Article  CAS  Google Scholar 

  • Litvin Y, Blanchard DC, Blanchard RJ (2007) Rat 22 kHz ultrasonic vocalizations as alarm cries. Behav Brain Res 182:166–172

    Article  PubMed  Google Scholar 

  • Maier EY, Ahrens AM, Ma ST, Schallert T, Duvauchelle CL (2010) Cocaine deprivation effect: cue abstinence over weekends boosts anticipatory 50-kHz ultrasonic vocalizations in rats. Behav Brain Res 214:75–79

    Article  PubMed  CAS  Google Scholar 

  • Meyer PJ, Ma ST, Robinson TE (2011) A cocaine cue is more preferred and evokes more frequency-modulated 50-kHz ultrasonic vocalizations in rats prone to attribute incentive salience to a food cue. Psychopharmacology (Berl) 219:999–1009

    Article  Google Scholar 

  • Mueller D, Perdikaris D, Stewart J (2002) Persistence and drug-induced reinstatement of a morphine-induced conditioned place preference. Behav Brain Res 136:389–397

    Article  PubMed  CAS  Google Scholar 

  • Nakamura H, Ishii K, Shimizu M (1978) Some altered responses in rats formerly dependent on morphine. Psychopharmacology (Berl) 56:269–277

    Article  CAS  Google Scholar 

  • Niel L, Weary DM (2006) Behavioural responses of rats to gradual-fill carbon dioxide euthanasia and reduced oxygen concentrations. Appl Anim Behav Sci 100:295–308

    Article  Google Scholar 

  • Panksepp J, Burgdorf J (2000) 50-kHz chirping (laughter?) in response to conditioned and unconditioned tickle-induced reward in rats: effects of social housing and genetic variables. Behav Brain Res 115:25–38

    Article  PubMed  CAS  Google Scholar 

  • Parker LA, Mcdonald RV (2000) Reinstatement of both a conditioned place preference and a conditioned place aversion with drug primes. Pharmacol Biochem Behav 66:559–561

    Article  PubMed  CAS  Google Scholar 

  • Parker LA, Limebeer CL, Slomke J (2006) Renewal effect: context-dependent extinction of a cocaine- and a morphine-induced conditioned floor preference. Psychopharmacology (Berl) 187:133–137

    Article  CAS  Google Scholar 

  • Parsons S (2000) Advantages and disadvantages of techniques for transforming and analyzing chiropteran echolocation calls. J Mammal 81:927–938

    Article  Google Scholar 

  • Pellow S, Chopin P, File SE, Briley M (1985) Validation of open:closed arm entries in an elevated plus-maze as a measure of anxiety in the rat. J Neurosci Meth 14:149–167

    Article  CAS  Google Scholar 

  • Robinson TE, Becker JB (1986) Enduring changes in brain and behavior produced by chronic amphetamine administration: a review and evaluation of animal models of amphetamine psychosis. Brain Res 396:157–198

    Article  PubMed  CAS  Google Scholar 

  • Rutten K, van der Kam EL, De VJ, Tzschentke TM (2011) Critical evaluation of the use of extinction paradigms for the assessment of opioid-induced conditioned place preference in rats. Pharmacology 87:286–296

    Article  PubMed  CAS  Google Scholar 

  • Sadananda M, Natusch C, Karrenbauer B, Schwarting RK (2012) 50-kHz calls in rats: effects of MDMA and the 5-HT(1A) receptor agonist 8-OH-DPAT. Pharmacol Biochem Behav 101:258–264

    Article  PubMed  CAS  Google Scholar 

  • Sales GD, Pye D (1974) Ultrasonic communication by animals. Chapman and Hall, London

    Book  Google Scholar 

  • Shoaib M, Stolerman IP, Kumar RC (1994) Nicotine-induced place preferences following prior nicotine exposure in rats. Psychopharmacology (Berl) 113:445–452

    Article  CAS  Google Scholar 

  • Siegel S, MacRae J (1984) Environmental specificity of tolerance. Trends Neurosci 7:140–143

    Article  Google Scholar 

  • Simola N, Ma ST, Schallert T (2009) Influence of acute caffeine on 50-kHz ultrasonic vocalizations in male adult rats and relevance to caffeine-mediated psychopharmacological effects. Int J Neuropsychopharmacol 13:123–132

    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

    Google Scholar 

  • Tzschentke TM (1998) Measuring reward with the conditioned place preference paradigm: a comprehensive review of drug effects, recent progress and new issues. Prog Neurobiol 56:613–672

    Article  PubMed  CAS  Google Scholar 

  • Tzschentke TM (2007) Measuring reward with the conditioned place preference (CPP) paradigm: update of the last decade. Addict Biol 12:227–462

    Article  PubMed  CAS  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

    PubMed  CAS  Google Scholar 

  • Vivian JA, Miczek KA (1991) Ultrasounds during morphine withdrawal in rats. Psychopharmacology (Berl) 104:187–193

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  • Williams SN, Undieh AS (2010) Brain-derived neurotrophic factor signaling modulates cocaine induction of reward-associated ultrasonic vocalization in rats. J Pharmacol Exp Ther 332:463–468

    Article  PubMed  CAS  Google Scholar 

  • Wohr M, Schwarting RK (2009) Ultrasonic communication in rats: effects of morphine and naloxone on vocal and behavioral responses to playback of 50-kHz vocalizations. Pharmacol Biochem Behav 94:285–295

    Article  PubMed  Google Scholar 

  • Wohr M, Schwarting RK (2010) Rodent ultrasonic communication and its relevance for models of neuropsychiatric disorders. e-Neuroforum 1:71–80

    Article  Google Scholar 

  • Wohr M, Houx B, Schwarting RK, Spruijt B (2008) Effects of experience and context on 50-kHz vocalizations in rats. Physiol Behav 93:766–776

    Article  PubMed  Google Scholar 

  • Wright JM, Gourdon JC, Clarke PB (2010) Identification of multiple call categories within the rich repertoire of adult rat 50-kHz ultrasonic vocalizations: effects of amphetamine and social context. Psychopharmacology (Berl) 211:1–13

    Article  CAS  Google Scholar 

  • Wright JM, Dobosiewicz MR, Clarke PB (2012) 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

    Article  PubMed  CAS  Google Scholar 

  • Zacny JP, Lichtor JL, Flemming D, Coalson DW, Thompson WK (1994) A dose–response analysis of the subjective, psychomotor and physiological effects of intravenous morphine in healthy volunteers. J Pharmacol Exp Ther 268:1–9

    PubMed  CAS  Google Scholar 

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Acknowledgments

This study was supported by a Natural Science and Engineering Research Council of Canada (NSERC) discovery grant (155055, to P.B.S.C), and an NSERC Postgraduate Scholarship D (to J.M.W). The authors thank Tina Scardochio for constructive comments on the manuscript. P.B.S.C. is a member of the Center for studies in Behavioral Neurobiology at Concordia University in Montreal. 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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  1. Department of Pharmacology and Therapeutics, McGill University, McIntyre Medical Building Rm. 1320, 3655 Promenade Sir William Osler, Montreal, QC, H3G 1Y6, Canada

    Jennifer M. Wright, Lan Deng & Paul B. S. Clarke

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  1. Jennifer M. Wright
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  2. Lan Deng
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  3. Paul B. S. Clarke
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Correspondence to Paul B. S. Clarke.

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Wright, J.M., Deng, L. & Clarke, P.B.S. Failure of rewarding and locomotor stimulant doses of morphine to promote adult rat 50-kHz ultrasonic vocalizations. Psychopharmacology 224, 477–487 (2012). https://doi.org/10.1007/s00213-012-2776-z

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