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Diazepam and gepirone selectively attenuate either 20–32 or 32–64 kHz ultrasonic vocalizations during aggressive encounters

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Abstract

Ultrasonic vocalizations (USV) in rats may communicate “affective” states, as they occur only in highly significant behavioral contexts such as during sex, aggression, exposure to painful or startling events. This proposal was evaluated in an experiment with adult male Long-Evans rats during agonistic encounters; specifically, the effects of diazepam, flumazenil and gepirone were studied on different types of USV emitted by intruder rats exposed to resident attacks and to “threat of attacks” (i.e., intruder protected within the home cage of the resident by a wire mesh cage). USV were readily emitted during agonistic encounters and consisted primarily of two distributions of pure tone whistles: 0.3- to 3-s, 20- to 32-kHz (“low”) signals and 0.02- to 0.3-s, 32- to 64-kHz (“high”) signals. A considerable repertoire of frequency modulated signals was observed and proved to be sensitive to the anxiolytic treatments. Diazepam (1–6 mg/kg) dose-dependently decreased high frequency USV during the threat of attack and decreased the mean pitch of the most predominant vocalizations but did not affect low frequency USV or the audible squeals (AS) in response to bites. Gepirone (0.3–6 mg/kg) dose-dependently decreased low frequency USV and did not affect high frequency USV or AS. Responses to thermal pain stimuli remained unaltered by all drugs, while walking duration was decreased and crouch postures were increased after diazepam but not after gepirone administration. Gepirone in the present dose range had minimal effects on submissive, exploratory and locomotor behaviors. The pattern of results is consistent with the proposal that low frequency USV reflect a heightened affective state which is ameliorated with 5HT1A but not benzodiazepine anxiolytics, and suggests that the suppression of high frequency USV in reaction to attacks or threats coincides with the sedative or muscle relaxant properties of these compounds.

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References

  • Baldessarini RJ (1985) Drugs and the treatment of psychiatric disorders. In: Gillman AG, Goodman LS, Rall TW, Murad F (eds) The pharmacological basis of therapeutics, 7th edn. MacMillan, New York, pp 387–445

    Google Scholar 

  • Blanchard DC, Hori K, Rodgers RJ, Hendrie CA, Blanchard RJ (1989) Attenuation of defensive threat and attack in wild rats (Rattus rattus) by benzodiazepines. Psychopharmacology 97[3]:392–401

    Google Scholar 

  • Blanchard DC, Blanchard RJ, Tom P, Rodgers RJ (1990a) Diazepam changes risk assessment in an anxiety/defense test battery. Psychopharmacology 101[4]:511–518

    Google Scholar 

  • Blanchard DC, Blanchard RJ, Rodgers RJ (1990b) Pharmacological and neural control of anti-predator defense in the rat. Aggress Behav 16[2]:165–175

    Google Scholar 

  • Charney DS, Woods SW, Krystal JH, Heninger GR (1990) Seroton-in function and human anxiety disorders. In: Whitaker-Asmitia PM, Peroutka SJ (eds) The neuropharmacology of serotonin. New York Academy of Sciences, New York, pp 558–573

    Google Scholar 

  • Cuomo V, Cagiano R, De Salvia MA, Maselli MA, Renna G, Racagni G (1988) Ultrasonic vocalization in response to unavoidable aversive stimuli in rats: effects of benzodiazepines. Life Sci 43:485–491

    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 

  • Gardner CR (1985) Distress vocalization in rat pups. A simple screening method for anxiolytic drugs. J Pharmacol Methods 14:181–187

    Google Scholar 

  • Gardner CR, Budhram P (1987) Effects of agents which interact with central benzodiazepine binding sites on stress-induced ultrasounds in rat pups. Eur J Pharmacol 134:275–283

    Google Scholar 

  • Hard E, Engel J (1988) Effects of 8-OH-DPAT on ultrasonic vocalization and audiogenic immobility reaction in pre-weanling rats. Neuropharmacology 27[10]:981–986

    Google Scholar 

  • Insel TR, Hill JL, Mayor RB (1986) Rat pup ultrasonic isolation calls: possible mediation by the benzodiazepine receptor complex. Pharmacol Biochem Behav 24[5]:1263–1267

    Google Scholar 

  • Kachigan SK (1986) Statistical analysis. Radius Press, New York

    Google Scholar 

  • Kaltwasser M (1990a) Startle-inducing acoustic stimuli evoke ultrasonic vocalization in the rat. Physiol Behav 48:13–17

    Google Scholar 

  • Kaltwasser M (1990b) Acoustic signaling in the Black rat (Rattus rattus). J Comp Psychol 104[3]:227–232

    Google Scholar 

  • Kaltwasser M (1991) Acoustic startle induced ultrasonic vocalization in the rat: a novel animal model of anxiety? Behav Brain Res 43:133–137

    Google Scholar 

  • Klein DF, Ross DC, Cohen P (1987) Panic and avoidance in agoraphobia. Arch Gen Psychiatry 44:377–385

    Google Scholar 

  • Korte SM, Smit J, Bouws GAH, Koolhaas JP, Bohus B (1990) Behavioral and neuroendocrine response to psychosocial stress in male rats: the effects of the 5-HT 1A agonist ipsapirone. Horm Behav 24:554–567

    Google Scholar 

  • Liebowitz MR, Fyer AJ, Gorman JM, Campeas R, Levin A, Davies SR, Goetz D, Klein DF (1986) Alprazolam in the treatment of panic disorders. J Clin Psychopharmacol 6[1]:13–20

    Google Scholar 

  • Martin JR, Pieri L, Bonetti EP, Schaffner R, Burkard WP, Cumin R, Haefely WE (1988) Ro 16-6028: a novel anxiolytic acting as a partial agonist at the benzodiazepine receptor. Pharmacopsychiatry 21:360–362

    Google Scholar 

  • Miczek KA (1979) A new test for aggression in rats without aversive stimulation: differential effects ofd-amphetamine and cocaine. Psychopharmacology 60[3]:253–259

    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, Thompson ML, Tornatzky W (1990) Short and long term physiological and neurochemical adaptations to social conflict. In: Puglisi-Allegra S, Oliviero A (eds) Psychobiology of stress. Kluwer, Netherlands, pp 15–30

    Google Scholar 

  • Miczek KA, Thompson ML, Tornatzky W (1991) Subordinate animals: behavioral and physiological adaptations and opioid tolerance. In: Brown M, Koob G, Rivier C (eds) Stress neurobiology and neuroendocrinology. Dekker, New York, pp 323–357

    Google Scholar 

  • Morgan MM, Levin ED, Liebskind JC (1987a) Characterization of the analgesic effects of the benzodiazepine antagonist, RO 15-1788. Brain Res 415:367–370

    Google Scholar 

  • Morgan MM, Levin ED, Liebskind JC (1987b) Diazepam dissociates the analgesic and aversive effects of periaqueductal gray stimulation in the rat. Brain Res 423:395–398

    Google Scholar 

  • Mos, J., van der Heyden, J. & Olivier, B. (1989) Behavioural effects of 5-HT3 antagonists in animal models for aggression, anxiety and psychosis. In: Bevan P, Cools AR, Archer T (eds) Behavioural pharmacology of 5-HT. Erlbaum, New Jersey, pp 389–396

    Google Scholar 

  • Mos J, van Logten J, Bloetjes K, Olivier B (1991) The effects of idazoxan and 8-OH-DPAT on sexual behaviour and associated ultrasonic vocalizations in the rat. Neurosci Biobehav Rev 15:505–510

    Google Scholar 

  • Nastiti K, Benton D, Brain PF (1991) The effects of compounds acting at the benzodiazepine receptor complex on the ultrasonic calling of mouse pups. Behav Pharmacol 2:121–128

    Google Scholar 

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

    Google Scholar 

  • Rodgers RJ, Hendrie CA (1983) Social conflict activates status-dependent endogenous analgesic and hyperalgesic mechanisms in male mice: effects of naloxone on nociception and behaviour. Physiol Behav 30[5]:775–780

    Google Scholar 

  • Rodgers RJ, Randall JI (1987) Social conflict analgesia: inhibition of early non-opioid component by diazepam or flumazenil fails to affect appearance of late opioid component. Brain Res Bull 19:141–144

    Google Scholar 

  • Rodgers RJ, Shepherd JK (1989) Prevention of the analgesic consequences of social defeat in male mice by 5-HT1A anxiolytics, buspirone, gepirone and ipsapirone. Psychopharmacology 99:374–380

    Google Scholar 

  • Rodgers RJ, Waters AJ (1984) Effects of the benzodiazepine antagonist Ro15-1788 on social and agonistic behaviour in male albino mice. Physiol Behav 33[3]:401–409

    Google Scholar 

  • Rodgers RJ, Waters AJ (1985) Benzodiazepines and their antagonists: a pharmacological analysis with particular reference to effects on “aggression”. Neurosci Biobehav Rev 9:21–35

    Google Scholar 

  • Scherer KR, Kappas A (1988) Primate vocal expression of affective state. In: Todt D, Goedeking P, Symmes D (eds) Primate vocal communication. Springer, Berlin Heidelberg New York, pp 171–194

    Google Scholar 

  • Schreiber R, De Vry J (1993) 5-HT1A receptor ligands in animal models of anxiety, impulsivity and depression: multiple mechanisms of action? Prog Neuropsychopharmacol Biol Psychiatry 17:87–104

    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 

  • Smith WJ (1979) The study of ultrasonic communication. Am Zool 19:531–538

    Google Scholar 

  • Taylor DP (1990) Serotonin agents in anxiety. Ann NY Acad Sci 600:545–557

    Google Scholar 

  • Tonoue T, Ashida Y, Makino H, Hata H (1986) Inhibition of shockelicited ultrasonic vocalization by opioid peptides in the rat: a psychotropic effect. Psychoneuroendocrinology 11[2]:177–184

    Google Scholar 

  • Tornatzky W, Miczek KA (1990) Behavior and telementered autonomic responses to clonidine, diazepam and social stress. Neurosci Abstr 16[1]:432

    Google Scholar 

  • Tornatzky W, Miczek KA (1991) Behavior and physiology of socially stressed rats: Anti- and pro-stress effects of anxiolytics. Neurosci Abstr 17[1]:147

    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[2]:147–148

    Google Scholar 

  • Vivian JA, Miczek KA (1990) Opioid suppression of distress ultrasounds after social defeat in rats. Neurosci Abstr 16[1]:443

    Google Scholar 

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

    Google Scholar 

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

    Google Scholar 

  • Winslow JT, Insel TR (1990) Serotonergic and catecholaminergic reuptake inhibitors have opposite effects on the ultrasonic isolation call of rat pups. Neuropsychopharmacology 3:51–59

    Google Scholar 

  • Winslow JT, Insel TR (1991a) Infant rat separation is a sensitive test for novel anxiolytics. Prog Neuropsychopharmacol Biol Psychiatry 15:745–757

    Google Scholar 

  • Winslow JT, Insel TR (1991b) The infant rat separation paradigm: a novel test for novel anxiolytics. TIPS 12:402–404

    Google Scholar 

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Vivian, J.A., Miczek, K.A. Diazepam and gepirone selectively attenuate either 20–32 or 32–64 kHz ultrasonic vocalizations during aggressive encounters. Psychopharmacology 112, 66–73 (1993). https://doi.org/10.1007/BF02247364

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  • DOI: https://doi.org/10.1007/BF02247364

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