Skip to main content
Log in

Effects of alpha-2 adrenoceptor antagonists on rough-and-tumble play in juvenile rats: evidence for a site of action independent of non-adrenoceptor imidazoline binding sites

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

Abstract

The pharmacological specificity of alpha-2 adrenoceptor involvement in the modulation of rough-and-tumble play behavior was assessed in juvenile rats. The alpha-2 adrenoceptor antagonists idazoxan and RX821002 both increased the frequency of pinning in individually housed rats that were given a brief opportunity to play. Dorsal contacts, a measure of play solicitation, were not consistently affected by these compounds. Since RX821002 shows little affinity for non-adrenoceptor imidazoline binding sites, it is likely that the facilitation of play following administration of these two compounds is due to blockade of alpha-2 receptors. The effect of RX821002 and idazoxan is unlikely to be an artifact associated with using rats that are reared in isolation, as RX821002 also increased pinning, as well as dorsal contacts, in group-housed rats that were isolated for a short period (4 h) before the play session. The alpha-1 adrenoceptor antagonist prazosin, which also binds to alpha-2B receptors, reduced the frequency of both pinning and dorsal contacts. There was a strong trend for St 587, a centrally active alpha-1 agonist, to attenuate the effect of prazosin on play. While this leaves open the possibility that prazosin may be reducing play through alpha-1 blockade, antagonist activity at alpha-2B receptors cannot be ruled out. From these data, we conclude that the facilitation of play following idazoxan and RX821002 is likely due to blockade of alpha-2A adrenoceptors. These findings add further support for a specific role of alpha-adrenoceptors in the modulation of playfulness in the juvenile rat.

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

  • Angulo JA, Printz D, Ledoux M, McEwen B (1991) Isolation stress increases tyrosine hydroxylase mRNA in the locus coeruleus and midbrain and decreases proenkephalin mRNA in the striatum and nucleus accumbens. Mol Brain Res 11:301–308

    Article  PubMed  Google Scholar 

  • Aston-Jones F, Bloom FE (1981) Activity of norepinephrine-containing locus coeruleus neurons in behaving rats anticipates fluctuations in the sleep-waking cycle. J Neurosci 1:876–886

    PubMed  Google Scholar 

  • Beatty WW, Costello KB, Berry SL (1984) Suppression of play fighting by aphetamine: effects of catecholamine antagonists, agonists and synthesis inhibitors. Pharmacol Biochem Behav 20:747–755

    Google Scholar 

  • Boyajian CL, Leslie FM (1987) Pharmacological evidence for alpha-2 adrenoceptor heterogeneity: differential binding properties of [3H]rauwolscine and [3H]idazoxan in rat brain. J Pharmacol Exp Ther 241:1092–1098

    PubMed  Google Scholar 

  • Boyajian CL, Loughlin SE, Leslie FM (1987) Anatomical evidence for alpha-2 adrenoceptor heterogeneity: differential autoradiographic distributions of [3H]rauwolscine and [3H]idazoxan in rat brain. J Pharmacol Exp Ther 241:1049–1091

    Google Scholar 

  • Braszko JJ, Wisniewski K (1990) α1 and α2-Adrenergic receptor blockade influences angiotensin II facilitation of avoidance behavior and stereotypy in rats. Psychoeuroendocrinology 15:239–252

    Article  Google Scholar 

  • Bylund DB (1985) Heterogeneity of alpha-2 adrenergic receptors. Pharmacol Biochem Behav 22:835–843

    Google Scholar 

  • Bylund DB, Ray-Prenger C, Murphy TJ (1988) Alpha-2A and alpha-2B adrenergic receptor subtypes: Antagonist binding in tissues and cell lines containing only one subtype. J. Pharmacol Exp Ther 245:600–607

    PubMed  Google Scholar 

  • Cambridge D, Davey MJ, Massingham R (1977) Prazosin, a selective antagonist of post-synaptic α-adrenoceptors. Br J Pharmacol 59:514P-515P

    Google Scholar 

  • Curet O, Dennis T, Scatton B (1987) Evidence for the involvement of presynaptic alpha-2 adrenoceptors in the regulation of norepinephrine metabolism in the rat brain. J Pharmacol Exp Ther 240:327–336

    PubMed  Google Scholar 

  • Dennis T, L'Heureux R, Carter C, Scatton B (1987) Presynaptic alpha-2 adrenoceptors play a major role in the effects of idazoxan on cortical noradrenaline release (as measured by in vivo dialysis) in the rat. J Pharmacol Exp Ther 241:642–649

    PubMed  Google Scholar 

  • DeJonge A, VanMeel JCA, Timmermans PBMWM, Van Zwieten PA (1981) A lipophilic, selective α1-adrenoceptor agonist: 2-(2-chloro-5-trifluoromethylphenylimino)imidazolidine (St. 587). Life Sci 28:2009–2016

    PubMed  Google Scholar 

  • Dettmar PW, Lynn AG, Tullock IF (1983) Neuropharmacological studies in rodents on the action of RX 781094, a new selective α2-adrenoceptor antagonist. Neuropharmacology 22:729–737

    Article  PubMed  Google Scholar 

  • Dickinson SL, Gadie B, Tulloch IF (1988) α1-and α2-Adrenoreceptor antagonists differentially influence locomotor and stereotyped behaviour induced by d-amphetamine and apomorphine in the rat. Psychopharmacology 96:521–527

    Google Scholar 

  • Fagen R (1981) Animal play behavior. Oxford University Press, New York

    Google Scholar 

  • Gobbi M, Frittoli E, Mennini T (1990) The modulation of [3H]noradrenaline and [3H]serotonin release from rat brain synaptosomes is not mediated by the α2B-adrenoceptor subtype. Naunyn-Schmiedeberg's Arch Pharmacol 342:382–386

    Article  Google Scholar 

  • Goldman CK, Marino L, Leibowitz SF (1985) Postsynaptic α-noradrenergic receptors mediate feeding induced by paraventricular nucleus injection of norepinephrine and clonidine. Eur J Pharmacol 115:11–19

    Article  PubMed  Google Scholar 

  • Herritch AJ, Henderson K, Westfall, TC (1990) Effects of social isolation on brain catecholamine and forced swuimming in rats: Prevention by antidepressant treatment. J Psychiatr Res 24:251–258

    Article  PubMed  Google Scholar 

  • Johnson RD, Minneman KP (1986) Characterization of α1-adrenoceptors which increase cyclic AMP accumulation in rat cerebral cortex. Eur J Pharmacol 129:293–305

    Article  PubMed  Google Scholar 

  • Langer SZ (1981) Presynaptic regulation of the release of catecholamines. Pharmacol Rev 32:337–362

    Google Scholar 

  • Langin D, Lafontan M, Stillings MR, Paris H (1989) [3H]RX821002: a new tool for the identification of α2A-adrenoceptors. Eur J Pharmacol 167:95–104

    Article  PubMed  Google Scholar 

  • Langin D, Paris H, Lafontan M (1990) Binding of [3H]idazoxan and of its methoxy derivative [3H]RX821002 in human fat cells: [3H]idazoxan but not [3H]RX821002 labels additional non-alpha2-adrenergic binding sites. Mol Pharmacol 37:876–885

    PubMed  Google Scholar 

  • Lehmann J, Koenig-Berard E, Vitou P (1989) The imidazoline-preferring receptor. Life Sci 45:1609–1615

    Article  PubMed  Google Scholar 

  • Marwaha J, Aghajanian GK (1982) Relative potencies of alpha-1 and alpha-2 antagonists in the locus ceruleus, dorsal raphe and dorsal lateral geniculate nuclei: An electrophysiological study. J Pharmacol Exp Ther 222:287–293

    PubMed  Google Scholar 

  • Mason ST (1984) Catecholamines and behaviour. Cambridge University Press, Cambridge

    Google Scholar 

  • Meany MJ, Stewart J (1981) A descriptive study of social development in the rat (Rattus norvegicus). Anim Behav 29:34–45

    Google Scholar 

  • Menkes DB, Baraban JM, Aghajanian GK (1981) Prazosin selectively antagonizes neuronal responses mediated by α1-adrenoceptors in brain. Naunyn-Schmiedeberg's Arch Pharmacol 317:273–275

    Article  Google Scholar 

  • Miach PJ, Dausse J-P, Cardot A, Meyer P (1980)3H-Prazosin binds specifically to α1-adrenoceptors in rat brain. Naunyn-Schmiedeberg's Arch Pharmacol 312:23–26

    Article  Google Scholar 

  • Montemayor ME, Clark AS, Lynn DM, Roy EJ (1990) Modulation by norepinephrine of neural responses to estradiol. Neuroendocrinology 42:473–480

    Google Scholar 

  • Nishikawa T, Kajiwara Y, Kono Y, Sono T, Nagasaki N, Tanaka M (1976) Different effects of social isolation on the levels of brain monoamines in post-weaning and young-adult rats. Folia Psych Neurol Japon 30:57–63

    Google Scholar 

  • Normansell L, Panksepp J (1985) Effects of clonidine and yohimbine on the social play of juvenile rats. Pharmacol Biochem Behav 22:881–883

    Google Scholar 

  • Oades RD (1985) The role of noradrenaline in tuning and dopamine in switching between signals in the CNS. Neurosci Biobehav Rev 9:261–282

    Google Scholar 

  • Pankseep J (1981) The ontogeny of play in rats. Dev Psychobiol 14:327–332

    Article  PubMed  Google Scholar 

  • Panksepp J, Siviy S, Normansell L (1984) The psychobiology of play: theoretical and methodological perspectives. Neurosci Biobehav Rev 8:465–492

    Google Scholar 

  • Panksepp J, Normansell L, Cox JF, Crepeau LJ, Sacks DS (1987) Psychopharmacology of social play. In Olivier B, Mos J, Brain PF (eds) Ethopharmacology of agonistic behaviour in animals and humans. Martinus Nijhoff Publishers, Dordrecht, Holland

    Google Scholar 

  • Pellis SM, Pellis V (1987) Play-fighting differs from serious fighting in both target of attack and tactics of fighting in the laboratory ratRattus norvegicus. Aggress Behav 13:227–242

    Google Scholar 

  • Pettibone DJ, Pfleuger AB, Totaro JA (1985) Comparison of the effects of recently developed α2-adrenergic antagonists with yohimbine and rauwolscine on monoamine synthesis in rat brain. Biochem Pharmacol 34:1093–1097

    Article  PubMed  Google Scholar 

  • Rossi J, Sahley TL, Panksepp J (1983) The role of brain norepinephrine in clonidine suppression of isolation-induced distress in the domestic chick. Psychopharmacology 79:338–339

    Google Scholar 

  • Routledge C, Marsden CA (1987) Comparison of the effects of selected drugs on the release of hypothalamic adrenaline and noradrenaline measured in vivo. Brain Res 426:103–111

    Article  PubMed  Google Scholar 

  • Ruffolo RR (1985) Selective α1-adrenoceptor agonists and antagonists. In: Szabadi E, Bradshaw CM, Nahorski SR (eds) Pharmacology of adrenoceptors. Macmillan, London

    Google Scholar 

  • Ruffolo RR, Waddell JE (1983) Aromatic and benzylic hydroxyl substitution of imidazolines and phenetylamines: differences in activity at alpha-1 and alpha-2 adrenergic receptors. J Pharmacol Exp Ther 224:559–566

    PubMed  Google Scholar 

  • Selden NRW, Robbins TW, Everitt BJ (1990) Enhanced behavioral conditioning to context and impaired behavioral and neuroendocrine responses to conditioned stimuli following ceruleocortical noradrenergic lesions: support for an attentional hypothesis of central noradrenergic function. J Neurosci 10:531–539

    PubMed  Google Scholar 

  • Siviy SM, Atrens DM (1992) The energetic costs of rough-and-tumble play in the juvenile rat. Dev Psychobiol 25:137–148

    Article  PubMed  Google Scholar 

  • Siviy SM, Panksepp J (1987) Sensory modulation of juvenile play in rats. Dev Psychobiol 20:39–55

    Article  PubMed  Google Scholar 

  • Siviy SM, Atrens DM, Menendez JA (1990) Idazoxan increases rough-and-tumble play, activity and exploration in juvenile rats. Psychopharmacology 100:119–123

    Google Scholar 

  • Starke K (1987) Presynaptic α-autoreceptors. Rev Physiol Biochem Pharmacol 107:73–146

    PubMed  Google Scholar 

  • Thiels E, Alberts JR, Cramer CP (1990) Weaning in rats: II. Pup behavior patterns. Dev Psychobiol 23:495–510

    Article  PubMed  Google Scholar 

  • Thor DH, Holloway WR (1984) Social play in juvenile rats: a decade of methodological and experimental research. Neurosci Biobehav Rev 8:455–464

    Google Scholar 

  • Toru M (1982) Increased tyrosine hydroxylase activity in frontal cortex of rats after long-term isolation stress. L'Encephale 8:315–317

    PubMed  Google Scholar 

  • U'Prichard DC, Charness ME, Robertson D, Snyder SH (1978) Prazosin: differential affinities for two populations of α-noradrenergic receptor binding sites. Eur J Pharmacol 50:87–89

    Article  PubMed  Google Scholar 

  • Walter DS, Flockhart IR, Haynes MJ, Howlett DR, Lane AC, Burton R, Johnson J, Dettmar, PW (1984) Effects of idazoxan on catecholamine systems in rat brain. Biochem Pharmacol 33:2553–2557

    Article  PubMed  Google Scholar 

  • Weinstock M, Speizer Z, Ashkenazi R (1978) Changes in brain catecholamine turnover and receptor sensitivity induced by social deprivation in rats. Psychopharmacology 56:205–209

    Google Scholar 

  • Winer BJ (1971) Statistical principles in experimental design. McGraw-Hill, New York

    Google Scholar 

  • Yang X-M, Gorman AL, Dunn AJ (1990) The involvement of central noradrenergic systems and corticotropin-releasing factor in defensive-withdrawal behavior in rats. J Pharmacol Exp Ther 255:1064–1070

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Siviy, S.M., Fleischhauer, A.E., Kuhlman, S.J. et al. Effects of alpha-2 adrenoceptor antagonists on rough-and-tumble play in juvenile rats: evidence for a site of action independent of non-adrenoceptor imidazoline binding sites. Psychopharmacology 113, 493–499 (1994). https://doi.org/10.1007/BF02245229

Download citation

  • Received:

  • Revised:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02245229

Key words

Navigation