Advertisement

Psychopharmacology

, Volume 112, Issue 1, pp 66–73 | Cite as

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

  • J. A. Vivian
  • K. A. Miczek
Original Investigations

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.

Key words

Ultrasonic vocalization Diazepam Gepirone Anxiolytics Aggression Affect 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 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 387–445Google Scholar
  2. 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]:392–401Google Scholar
  3. Blanchard DC, Blanchard RJ, Tom P, Rodgers RJ (1990a) Diazepam changes risk assessment in an anxiety/defense test battery. Psychopharmacology 101[4]:511–518Google Scholar
  4. Blanchard DC, Blanchard RJ, Rodgers RJ (1990b) Pharmacological and neural control of anti-predator defense in the rat. Aggress Behav 16[2]:165–175Google Scholar
  5. 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 558–573Google Scholar
  6. 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 43:485–491Google Scholar
  7. d'Amour F, Smith D (1941) A method for determining loss of pain sensation. J Pharmacol Exp Ther 72:74–79Google Scholar
  8. Gardner CR (1985) Distress vocalization in rat pups. A simple screening method for anxiolytic drugs. J Pharmacol Methods 14:181–187Google Scholar
  9. 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 134:275–283Google Scholar
  10. Hard E, Engel J (1988) Effects of 8-OH-DPAT on ultrasonic vocalization and audiogenic immobility reaction in pre-weanling rats. Neuropharmacology 27[10]:981–986Google Scholar
  11. Insel TR, Hill JL, Mayor RB (1986) Rat pup ultrasonic isolation calls: possible mediation by the benzodiazepine receptor complex. Pharmacol Biochem Behav 24[5]:1263–1267Google Scholar
  12. Kachigan SK (1986) Statistical analysis. Radius Press, New YorkGoogle Scholar
  13. Kaltwasser M (1990a) Startle-inducing acoustic stimuli evoke ultrasonic vocalization in the rat. Physiol Behav 48:13–17Google Scholar
  14. Kaltwasser M (1990b) Acoustic signaling in the Black rat (Rattus rattus). J Comp Psychol 104[3]:227–232Google Scholar
  15. Kaltwasser M (1991) Acoustic startle induced ultrasonic vocalization in the rat: a novel animal model of anxiety? Behav Brain Res 43:133–137Google Scholar
  16. Klein DF, Ross DC, Cohen P (1987) Panic and avoidance in agoraphobia. Arch Gen Psychiatry 44:377–385Google Scholar
  17. 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 24:554–567Google Scholar
  18. 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]:13–20Google Scholar
  19. 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 21:360–362Google Scholar
  20. Miczek KA (1979) A new test for aggression in rats without aversive stimulation: differential effects ofd-amphetamine and cocaine. Psychopharmacology 60[3]:253–259Google Scholar
  21. 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 110:379–382Google Scholar
  22. 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 15–30Google Scholar
  23. 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 323–357Google Scholar
  24. Morgan MM, Levin ED, Liebskind JC (1987a) Characterization of the analgesic effects of the benzodiazepine antagonist, RO 15-1788. Brain Res 415:367–370Google Scholar
  25. Morgan MM, Levin ED, Liebskind JC (1987b) Diazepam dissociates the analgesic and aversive effects of periaqueductal gray stimulation in the rat. Brain Res 423:395–398Google Scholar
  26. 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 389–396Google Scholar
  27. 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 15:505–510Google Scholar
  28. 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 2:121–128Google Scholar
  29. Nyby J, Whitney G (1978) Ultrasonic communication of adult myomorph rodents. Neurosci Biobehav Rev 2:1–14Google Scholar
  30. 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]:775–780Google Scholar
  31. 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 19:141–144Google Scholar
  32. 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 99:374–380Google Scholar
  33. 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]:401–409Google Scholar
  34. Rodgers RJ, Waters AJ (1985) Benzodiazepines and their antagonists: a pharmacological analysis with particular reference to effects on “aggression”. Neurosci Biobehav Rev 9:21–35Google Scholar
  35. 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 171–194Google Scholar
  36. 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 17:87–104Google Scholar
  37. Shepherd JK, Blanchard DC, Weiss SM, Rodgers RJ, Blanchard RJ (1992) Morphine attenuates antipredator ultrasonic vocalizations in mixed-sex rat colonies. Pharmacol Biochem Behav 41:551–558Google Scholar
  38. Smith WJ (1979) The study of ultrasonic communication. Am Zool 19:531–538Google Scholar
  39. Taylor DP (1990) Serotonin agents in anxiety. Ann NY Acad Sci 600:545–557Google Scholar
  40. 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]:177–184Google Scholar
  41. Tornatzky W, Miczek KA (1990) Behavior and telementered autonomic responses to clonidine, diazepam and social stress. Neurosci Abstr 16[1]:432Google Scholar
  42. Tornatzky W, Miczek KA (1991) Behavior and physiology of socially stressed rats: Anti- and pro-stress effects of anxiolytics. Neurosci Abstr 17[1]:147Google Scholar
  43. 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]:147–148Google Scholar
  44. Vivian JA, Miczek KA (1990) Opioid suppression of distress ultrasounds after social defeat in rats. Neurosci Abstr 16[1]:443Google Scholar
  45. Vivian JA, Miczek KA (1991) Ultrasounds during morphine withdrawal in rats. Psychopharmacology 104:187–193Google Scholar
  46. Vivian JA, Miczek KA (1993) Morphine attenuates ultrasonic vocalizations during agonistic encounters in adult rats. Psychopharmacology 111:367–375Google Scholar
  47. Winslow JT, Insel TR (1990) Serotonergic and catecholaminergic reuptake inhibitors have opposite effects on the ultrasonic isolation call of rat pups. Neuropsychopharmacology 3:51–59Google Scholar
  48. Winslow JT, Insel TR (1991a) Infant rat separation is a sensitive test for novel anxiolytics. Prog Neuropsychopharmacol Biol Psychiatry 15:745–757Google Scholar
  49. Winslow JT, Insel TR (1991b) The infant rat separation paradigm: a novel test for novel anxiolytics. TIPS 12:402–404Google Scholar

Copyright information

© Springer-Verlag 1993

Authors and Affiliations

  • J. A. Vivian
    • 1
  • K. A. Miczek
    • 1
  1. 1.Department of PsychologyTufts UniversityMedfordUSA

Personalised recommendations