Skip to main content
Log in

Ultrasounds emitted by female rats during agonistic interactions: effects of morphine and naltrexone

  • Original Investigations
  • Published:
Psychopharmacology Aims and scope Submit manuscript

Abstract

Ultrasonic vocalizations may be an expression of the affective pain response in laboratory rodents. The present experiment compared morphine's effects on high (33–60 kHz) and low (20–32 kHz) frequency ultrasonic vocalizations to its effects on a range of unconditioned behavioral responses to aversive stimuli; the influence of estrous cyclicity on morphine sensitivity was also investigated. In experiment 1, naive female Long-Evans rats, selected during estrus or diestrus, received cumulative morphine (1, 3, 6, 10 mg/kg SC) or saline, and in experiment 2, rats were pretreated with naltrexone (0.1 mg/kg IP) 5 min before morphine (17, 30, 60, 100 mg/kg SC). The following endpoints were measured 20–25 min post-injection: (1) tail flick latency; (2) ultrasonic and audible vocalizations; (3) the behavioral response to aggressive attack; and (4) locomotor activity. Following a brief exposure to an attack, rats were threatened by an aggressor but protected from further attack by a wire mesh cage (30×21.5×20 cm), thereby allowing for continued behavioral and vocal measurement without the risk of physical injury; video and audio recordings were made of the attack encounter and a subset of the protected encounter (1 min). The endpoint most potently and specifically modulated by morphine was high frequency ultrasounds. The rate of high frequency calling varied as a function of the estrous cycle, supporting gonadal hormone modulation of ultrasonic vocalizations. Low frequency ultrasounds, by contrast, were relatively insensitive to opiate manipulation and were less influenced by estrous cyclicity. High frequency vocalizations may be a more sensitive indication of the affective response to an attacking conspecific than low frequency calls. The attenuation of high frequency ultrasonic calls at doses that do not affect any other behavioral or vocal responses may correspond to human descriptions of morphine analgesia, in which the affective component to pain is more potently modulated than the sensory component.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Bandler R (1988) Brain mechanisms of aggression as revealed by electrical and chemical stimulation: suggestion of a central role for the midbrain periaqueductal grey region. In: Epstein AN, Morrison AR (eds) Progress in psychobiology and physiological psychology. Academic Press, New York, pp 67–154

    Google Scholar 

  • Beatty WW, Fessler RG (1976) Ontogeny of sex differences in open-field behavior and sensitivity to electric shock in the rat. Physiol Behav 16:413–417

    Google Scholar 

  • Beatty WW, Fessler RG (1977) Gonadectomy and sensitivity to electric shock in the rat. Physiol Behav 19:1–6

    Google Scholar 

  • Berg DS, Baenninger R (1973) Hissing by laboratory rats during fighting encounters. Behav Biol 8:733–741

    Google Scholar 

  • Blanchard DC, Blanchard RJ, Rodgers RJ (1990) Pharmacological and neural control of anti-predator defense in the rat. Aggress Behav 16:165–175

    Google Scholar 

  • Blanchard RJ, Blanchard DC, Agullana R, Weiss S (1991a) Twenty-two kHz alarm cries to presentation of a predator, by laboratory rats living in visible burrow systems. Physiol Behav 50:967–972

    Google Scholar 

  • Blanchard DC, Weatherspoon A, Shepherd J, Rodgers RJ, Weiss SM, Blanchard RJ (1991b) “Paradoxical” effects of morphine on antipredator defense reactions in wild and laboratory rats. Pharmacol Biochem Behav 40:819–828

    Google Scholar 

  • Blanchard RJ, Agullana R, McGee L, Weiss S, Blanchard DC (1992a) Sex differences in the incidence and sonographic characteristics of antipredator ultrasonic cries in the laboratory rat (Rattus norvegicus). J Comp Psychol 106:270–277

    Google Scholar 

  • Blanchard RJ, Weiss SM, Yudko EB, Taukulis HK (1992b) Social encounters with conspecifics elicit selective high frequency (35–70 kHz) ultrasonic vocalizations in rats. Soc Neurosci Abstr 18:872

    Google Scholar 

  • Blumberg MS (1992) Ultrasonic short calls: locomotion, biomechanics and communication. J Comp Psychol 106:360–365

    Google Scholar 

  • Bornschein RL, Crockett RS, Smith RP (1977) Diurnal variations in the analgesic effectiveness of morphine in mice. Pharmacol Biochem Behav 6:621–626

    Google Scholar 

  • Brudzynski SM, Ociepa D (1992) Ultrasonic vocalization of laboratory rats in response to handling and touch. Physiol Behav 52:655–660

    Google Scholar 

  • Candido J, Lutfy K, Billings B, Sierra V, Duttaroy A, Inturrisi CE, Yoburn BC (1992) Effect of adrenal and sex hormones on opioid analgesia and receptor regulation. Pharmacol Biochem Behav 42:685–692

    Google Scholar 

  • Cuomo V, Cagiano R, Desalvia MA, Restani P, Galimberti R, Racagni G, Galli CL (1988) Ultrasonic vocalization in rat pups as a marker of behavioral development: an investigation of the effects of drugs influencing brain opioid systems. Neurotoxicol Teratol 10:465–469

    Google Scholar 

  • D'Amour F, Smith D (1941) A method for determining loss of pain sensation. J Pharmacol Exp Ther 72:74–79

    Google Scholar 

  • Depaulis A, Keay K, Bandler R (1992) Longitudinal neuronal organization of defensive reactions in the midbrain periaqueductal gray region of the rat. Exp Brain Res 90:307–318

    Google Scholar 

  • Dewey WL, Harris LS (1975) The tail-flick test. In: Neidle A, Ehrenpress S (eds) Methods in narcotics research. Dekker, New York, pp 101–109

    Google Scholar 

  • Floody OR, Pfaff DW (1977) Communication among hamsters by high-frequency acoustic signals: I. Physical characteristics of hamster calls. J Comp Physiol Psychol 91:794–806

    Google Scholar 

  • Franklin KBJ (1989) Analgesia and the neural substrate of reward. Neurosci Biobehav Rev 18:149–154

    Google Scholar 

  • Haney M, Miczek KA (1993) Ultrasounds during agonistic interactions between female rats (Rattus norvegicus). J Comp Psychol (in press)

  • Innes DG, Kavaliers M (1987) Opiates and deer mouse behavior: differences between island and mainland populations. Can J Zool 65:2504–2512

    Google Scholar 

  • Jürgens U, Pratt R (1979) Role of the periaqueductal gray in vocal expression of emotion. Brain Res 167:367–378

    Google Scholar 

  • Kafka MS, Wirz-Justice A, Naber D, Moore RY, Benedito MA (1983) Circadian rhythms in rat brain neurotransmitter receptors. Fed Proc 42:2796–2801

    Google Scholar 

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

    Google Scholar 

  • Kasson BG, George R (1984) Endocrine influences on the actions of morphine IV. Effects of sex and strain. Life Sci 34:1627–1634

    Google Scholar 

  • Kepler KL, Kest B, Kiefel JM, Cooper ML, Bodnar RJ (1989) Roles of gender, gonadectomy and estrous phase in the analgesic effects of intraventricular morphine in rats. Pharmacol Biochem Behav 34:119–127

    Google Scholar 

  • Kepler KL, Standifer KM, Paul D, Kest B, Pasternak GW, Bodnar RJ (1991) Gender effects and central opioid analgesia. Pain 45:87–94

    Google Scholar 

  • King FA (1986) Philosophical and practical issues in animal research involving pain and stress. Ann NY Acad Sci 467:405–409

    Google Scholar 

  • Kirk RE (1982) Experimental design. Wadsworth, Belmont, Ca., pp 95–97

    Google Scholar 

  • Mansour A, Khachaturian H, Lewis ME, Akil H, Watson HJ (1988) Anatomy of CNS opioid receptors. Trends Neurosci 7:308–314

    Google Scholar 

  • Miczek KA (1982) Ethological analysis of drug action on aggression, defense and defect. In: Spiegelstein Y, Levy A (eds) Behavioral models and the analysis of drug action. Amsterdam: Elsevier, pp 225–239

    Google Scholar 

  • Miczek KA, Vivian JA (1993) Automatic quantification of withdrawal from 5-day diazepam in rats: ultrasonic distress vocalizations and hyperreflexia to acoustic startle stimuli. Psychopharmacology 110:379–382

    Google Scholar 

  • Miczek KA, Tornatzky W, Vivian J (1991) Ethology and neuropharmacology: rodent ultrasounds. In: Olivier B, Mos J, Slangen J (eds) Animal models in psychopharmacology: advances in pharmacological sciences. Birkhauser, Basel, pp 409–427

    Google Scholar 

  • Miczek KA, Weerts EM, Tornatzky W, DeBold JF, Vatne TM (1992) Alcohol and “bursts” of aggressive behavior: ethological analysis of individual differences in rats. Psychopharmacology 107:551–563

    Google Scholar 

  • Nyby J, Whitney G (1978) Ultrasonic communication of adult myomorph rodents. Neurosci Biobehav Rev 2:1–14

    Google Scholar 

  • Sales GD (1972) Ultrasound and aggressive behavior in rats and other small mammals. Anim Behav 20:88–100

    Google Scholar 

  • Schmauss C (1987) Spinal k-opioid receptor-mediated antinociception is stimulus-specific. Eur J Pharmacol 137:197–205

    Google Scholar 

  • Schmauss C, Yaksh TL (1984) In vivo studies on spinal opiate receptor systems mediating antinociception. II. Pharmacological profiles suggesting a differential association of mu, delta and kappa receptors with visceral chemical and cutaneous thermal stimuli in the rat. J Pharmacol Exp Ther 228:1–12

    Google Scholar 

  • Shepherd JK, Blanchard DC, Weiss SM, Rodgers RJ, Blanchard RJ (1992) Morphine attenuates antipredator ultrasonic vocalizations in mixed-sex rat colonies. Pharmacol Biochem Behav 41:551–558

    Google Scholar 

  • Sewell GD (1967) Ultrasound in adult rodents. Nature 215:512

    Google Scholar 

  • Takahashi LK, Thomas DA, Barfield R (1983) Analysis of ultrasonic vocalizations emitted by residents during aggressive encounters among rats (Rattus norvegicus). J Comp Psychol 97:207–212

    Google Scholar 

  • Tallarida RJ, Murray RB (1987) Manual of pharmacologic calculations with computer programs. Springer, New York, pp 19–22, 153–159

    Google Scholar 

  • Thomas DA, Takahashi LK, Barfield RJ (1983) Analysis of ultrasonic vocalization emitted by intruders during aggressive encounters among rats (Rattus norvegicus). J Comp Psychol 97:201–206

    Google Scholar 

  • Tonoue T, Ashida Y, Makinott H, Hata H (1986) Inhibition of shock-elicited ultrasonic vocalization by opioid peptides in the rat: a psychotropic effect. Psychoneuroendocrinology 11:177–184

    Google Scholar 

  • Van der Poel AM, Miczek KA (1991) Long ultrasonic calls in male rats following mating, defeat and aversive stimulation: frequency modulation and bout structure. Behaviour 119:127–142

    Google Scholar 

  • Van der Poel AM, Noach EJK, Miczek KA (1989) Temporal patterning of ultrasonic distress calls in the adult rat: effects of morphine and benzodiazepines. Psychopharmacology 97:147–148

    Google Scholar 

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

    Google Scholar 

  • Vivian JA, Miczek KA (1993a) Morphine attenuates ultrasonic vocalizations during agonistic encounters in adult rats. Psychopharmacology 111:66–73

    Google Scholar 

  • Vivian JA, Miczek KA (1993b) Diazepam and gepirone selectively attenuate either 20–32 or 32–64 kHz ultrasonic vocalizations during aggressive encounters. Psychopharmacology 112:66–73

    Google Scholar 

  • Wenger GR (1980) Cumulative dose-response curves in behavioral pharmacology. Pharmacol Biochem Behav 13:647–651

    Google Scholar 

  • Wetzel DM, Kelley DB, Campbell BA (1980) Central control of ultrasonic vocalizations in neonatal rats: I. Brain stem motor nuclei. J Comp Physiol Psychol 94:596–605

    Google Scholar 

  • Wikler A (1950) Sites and mechanisms of action of morphine and related drugs in the central nervous system. Pharmacol Rev 2:435–506

    Google Scholar 

  • Wilkinson LO, Dourish CT (1991) Serotonin and animal behavior. In: Peroutka SR (ed) Serotonin receptor subtypes: basic and clinical aspects. Wiley-Liss, New York, pp 147–210

    Google Scholar 

  • Yajima Y, Hayashi Y, Yoshii N (1980) The midbrain central gray substance as a highly sensitive neural structure for the production of ultrasonic vocalization in the rat. Brain Res 198:446–452

    Google Scholar 

  • Yaksh TL, Rudy TA (1978) Narcotic analgetics: CNS sites and mechanisms of action as revealed by intracerebral injection techniques. Pain 4:299–359

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Haney, M., Miczek, K.A. Ultrasounds emitted by female rats during agonistic interactions: effects of morphine and naltrexone. Psychopharmacology 114, 441–448 (1994). https://doi.org/10.1007/BF02249334

Download citation

  • Received:

  • Revised:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02249334

Key words

Navigation