Skip to main content
Log in

Comparative effects ofβ 2-adrenoceptor agonists on intracranial self-stimulation, Sidman avoidance, and motor activity in rats

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

Abstract

The effects of β-adrenoceptor agonists were compared in various operant behavioral tasks, particularly intracranial self-stimulation (ICSS). Clenbuterol, salbutamol, and terbutaline all reduced responding by rats that lever-pressed for low stimulation intensities. The effects of clenbuterol in this test were completely reversed by propranolol, and those of salbutamol were partly reversed. Intermediate doses of clenbuterol and salbutamol slowed the initiation of rewarding brain stimulation in a shuttlebox but had little or no effect on the termination latencies. However, higher doses of both drugs lengthened the termination latencies. Motor activity was reduced at doses that attenuated ICSS responding. Complete tolerance occurred within 4 days to the effects of clenbuterol and salbutamol on leverpressing ICSS and to the effects of clenbuterol on motor activity. The apparent performance deficits induced by these drugs were overcome by more intense motivation. For example, even at high doses, clenbuterol reduced ICSS leverpressing only partially when animals bar-pressed for high rather than low stimulation intensities. Furthermore, all three drugs failed to alter Sidman avoidance responding at doses up to 100 times those that attenuated ICSS responding. It is concluded that although β-adrenoceptor agonists cause apparent sedation in rats, this sedation is limited and shows rapid tolerance.

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

  • Atrens DM, Ljungberg T, Ungerstedt U (1976) Modulation of reward and aversion processes in the rat diencephalon by neuroleptics: differential effects of clozapine and haloperidol. Psychopharmacology 49:97–100

    Google Scholar 

  • Banerjee SP, Kung LS, Riggi SJ, Chanda SK (1977) Development of β-adrenergic receptor subsensitivity by antidepressants. Nature 268:455–456

    Google Scholar 

  • Barlow RE, Bartholomew DJ, Bremner JM, Brunk HD (1972) Statistical inference under order restrictions. Wiley, New York, pp 183–188

    Google Scholar 

  • Borsini F, Bendotti C, Thurlby P, Samanin R (1982) Evidence that systemically administered salbutamol reduces food intake in rats by acting on central beta-adrenergic sites. Life Sci 30:905–911

    Google Scholar 

  • Brown MB, Forsythe AB (1974) The small sample behavior of some statistics which test the equality of several means. Technometrics 16:129–132

    Google Scholar 

  • Fenton HM, Liebman JM (1982) Intracranial self-stimulation response decrement patterns differentiate drug-induced performance deficit from effects on reward. Pharmacol Biochem Behav 17:1207–1212

    Google Scholar 

  • Frances H, Puech AJ, Simon P (1978) Profil psychopharmacologique de l'isoprenaline et du salbutamol. J Pharmacol 9:25–34

    Google Scholar 

  • Games PA, Howell JF (1976) Pairwise multiple comparison procedures with unequal n's and/or variances: a Monte Carlo study. J Educ Stat 1:113–125

    Google Scholar 

  • Hall H, Sallemark M, Ross SB (1980) Clenbuterol: a central β-adrenoceptor agonist. Acta Pharmacol Toxicol (Copenh) 47:159–160

    Google Scholar 

  • Konig JFR, Klippel RA (1963) The rat brain, Krieger, Huntington, NY

    Google Scholar 

  • LeCrubier Y, Puech AJ, Jouvent R, Simon P, Widlocher D (1980) A beta-adrenergic stimulant (salbutamol) versus clomipramine in depression: a controlled study. Br J Psychiatry 136:354–358

    Google Scholar 

  • Levene H (1960) Robust tests for equality of variance. In: Olkin I (ed) Contributions to probability and statistics. Stanford University Press, Palo Alto, CA pp 278–292

    Google Scholar 

  • Liebman JM (1982) Understanding neuroleptics: from “anhedonia” to “neuroleptothesia”. Behav Brain Sci 5:64–65

    Google Scholar 

  • Liebman JM (1983) Discriminating between reward and performance: a critical review of intracranial self-stimulation methodology. Neurosci Biobehav Rev 7:45–72

    Google Scholar 

  • Liebman JM, Hall N, Prowse J (1982) Effects of various catecholamine receptor antagonists, muscle relaxation and physical hindrance on shuttlebox self-stimulation. Pharmacol Biochem Behav 16:785–790

    Google Scholar 

  • Mogilnicka E (1982) The effects of acute and repeated treatment with salbutamol, a β-adrenoceptor agonist, on clonidine-induced hypoactivity in rats. J Neural Transm 53:117–126

    Google Scholar 

  • Muller M, Mogilnicka E (1981) Influence of salbutamol and other β-agonists on hypothermia induced by clonidine, apomorphine and reserpine in mice. J Neural Transm 52:259–267

    Google Scholar 

  • Ortmann R, Martin S, Radeke E, Delini-Stula A (1981) Interaction of β-adrenoceptor agonists with the serotonergic system in rat brain: a behavioral study using thel-5-HTP syndrome. Naunyn-Schmiedeberg's Arch Pharmacol 316:225–230

    Google Scholar 

  • Prowse J, Noreika L, Gerhardt S, Liebman J (1981) Selective attenuation of intracranial self-stimulation by the beta2-agonist, salbutamol. Fed Proc 40:293

    Google Scholar 

  • Przegalinski E, Baran L, Kedrek G (1980) The central action of salbutamol, a β-agonist with a potential antidepressant activity. Pol J Pharmacol Pharm 32:485–493

    Google Scholar 

  • Ross SB (1980) Antagonism of reserpine-induced hypothermia in mice by some β-adrenoceptor agonists. Acta Pharmacol Toxicol (Copenh) 47:347–350

    Google Scholar 

  • Sugrue MF (1982) A study of the effects of chronic salbutamol on rat brain monoaminergic systems. J Pharm Pharmacol 34:446–449

    Google Scholar 

  • Sulser F (1978) Functional aspects of the norepinephrine receptor coupled adenylate cyclase system in the limbic forebrain and its modification by drugs which precipitate or alleviate depression: molecular approaches to an understanding of affective disorders. Pharmacopsychiatry 11:43–52

    Google Scholar 

  • Waldmeier PC (1981) Stimulation of central serotonin turnover by β-adrenoceptor agonists. Naunyn-Schmiedeberg's Arch Pharmacol 317:115–119

    Google Scholar 

  • Winer BJ (1962) Statistical principles in experimental design (2. edn). McGraw-Hill, New York, pp 196–201

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Liebman, J.M., Hall, N.R., Prowse, J. et al. Comparative effects ofβ 2-adrenoceptor agonists on intracranial self-stimulation, Sidman avoidance, and motor activity in rats. Psychopharmacology 84, 336–341 (1984). https://doi.org/10.1007/BF00555209

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00555209

Key words

Navigation