Advertisement

Psychopharmacology

, Volume 96, Issue 4, pp 521–527 | Cite as

α1- and α2-Adrenoreceptor antagonists differentially influence locomotor and stereotyped behaviour induced byd-amphetamine and apomorphine in the rat

  • Stephen L. Dickinson
  • Brian Gadie
  • Ian F. Tulloch
Original Investigations

Abstract

The importance of dopamine (DA) in mediating locomotor, exploratory and stereotyped behaviour in rodents is well established. Evidence also indicates a modulatory role for noradrenaline (NA) although, due to non-specificity of previously available agents, a precise role remains undefined. The effects of the specific and selective α-adrenoreceptor antagonists idazoxan (α2) and prazosin (α1) on behaviour induced by amphetamine and apomorphine have been investigated in the rat.d-Amphetamine (2 mg/kg) induced hyperactive locomotion and exploration. Pretreatment with prazosin (1 mg/kg) markedly reduced these responses. In contrast, pretreatment with idazoxan (20 mg/kg) only marginally alteredd-amphetamine hyperactivity. Apomorphine (0.5 mg/kg) induced biphasic locomotor and exploratory activity. Neither α-antagonist affected the initial burst of activity (60 min), although prazosin inhibited whereas idazoxan potentiated the secondary phase (90–180 min). At higher dosage, amphetamine (6 mg/kg) and apomorphine (2 mg/kg) induced stereotyped behaviours. Prazosin pretreatment enhanced stereotyped gnawing and decreased sniffing and locomotion, whereas idazoxan increased locomotion and decreased amphetamine-induced mouth movements. These data indicate that DA-induced locomotor and stereotyped behaviours are differentially influenced (in opposite directions) by both α1- and α2-adrenoreceptor antagonists. NA may thus modulate the expression and character of behaviour by influencing DA function in certain brain areas.

Key words

α-Adrenoreceptor antagonists Dopamine Noradrenaline Behaviour Amphetamine Apomorphine 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Anden NE, Pauksens K, Svensson K (1982) Selective blockade of brain α2-autoreceptors by yohimbine: effects on motor activity and on turnover of noradrenaline and dopamine. J Neural Transm 55:111–120PubMedGoogle Scholar
  2. Clineschmidt BV, Flataker LM, Faison E, Holmes R (1979) An in vivo model for investigating α1- and α2-receptors in the CNS: studies with mianserin. Arch Int Pharmacodyn Ther 242:59–76PubMedGoogle Scholar
  3. Costall B, Naylor RJ, Pinder RM (1976) Characterisation of the mechanisms for hyperactivity induction from the nucleus accumbens by phenylethylamine derivatives. Psychopharmacology 48:225–231PubMedGoogle Scholar
  4. Costall B, Marsden CD, Naylor RJ, Pycock CJ (1977) Stereotyped behaviour patterns and hyperactivity induced by amphetamine and apomorphine after discrete 6-hydroxydopamine lesions of extrapyramidal and mesolimbic nuclei. Brain Res 123:89–11PubMedGoogle Scholar
  5. Creese I, Iversen SD (1975) The pharmacological and anatomical substrates of the amphetamine response in the rat. Brain Res 83:419–436PubMedGoogle Scholar
  6. Delini-Stula A, Baumann P, Buch O (1979) Depression of exploratory activity by clonidine in rats as a model for the detection of relative pre- and postsynaptic central noradrenergic receptor selectivity of α-adrenolytic drugs. Naunyn Schmiedeberg's Arch Pharmacol 307:115–122Google Scholar
  7. Dickinson SL, Curzon G (1983) Roles of dopamine and 5-hydroxytryptamine in stereotyped and non-stereotyped behaviour. Neuropharmacology 22:805–812PubMedGoogle Scholar
  8. Dickinson SL, Gadie B, Tulloch IF (1986) Differential effects of specific α-adrenoreceptor antagonists on catecholamine mediated behaviour. Br J Pharmacol 89:872PGoogle Scholar
  9. Drew GM, Gower AJ, Marriott AS (1979) α2-Adrenoreceptors mediate clonidine-induced sedation in the rat. Br J Pharmacol 67:133–141PubMedGoogle Scholar
  10. Grabowska-Anden M (1977) Modification of the amphetamine-induced stereotypy in rats following inhibition of the noradrenaline release by FLA 136. J Pharm Pharmacol 29:566–567PubMedGoogle Scholar
  11. Heal DJ (1984) Phenylephrine-induced activity in mice as a model of central α1-adrenoceptor function. Neuropharmacology 23:1241–1251PubMedGoogle Scholar
  12. Jackson DM, Anden N-E, Dahlstrom A (1975) A functional effect of dopamine in the nucleus accumbens and in some other dopamine-rich parts of the rat brain. Psychopharmacology 45:139–149Google Scholar
  13. Kelly PH, Seviour PW, Iversen SD (1975) Amphetamine and apomorphine responses in the rat following 6-OHDA lesions of the nucleus accumbens septi and corpus striatum. Brain Res 94:507–522PubMedGoogle Scholar
  14. Kostowski W, Jerlicz, M, Bidzinski A, Hauptmann M (1978) Evidence for existence of two opposite noradrenergic brain systems controlling behaviour. Psychopharmacology 59:311–312PubMedGoogle Scholar
  15. Maj J, Sowinska M, Kapturkiewicz Z, Sarnek J (1972) The effect ofl-dopa and (+)-amphetamine on the locomotor activity after pimozide and phenoxybenzamine. J Pharm Pharmacol 24:412–413PubMedGoogle Scholar
  16. Makanjuola ROA, Dow RC, Ashcroft GW (1980) Behavioural responses to stereotactically controlled injections of monoamine neurotransmitters into the accumbens and caudate-putamen nuclei. Psychopharmacology 71:227–235PubMedGoogle Scholar
  17. Mogilnicka E, Braestrup C (1976) Noradrenergic influence on the stereotyped behaviour induced by amphetamine, phenethylamine and apomorphine. J Pharm Pharmacol 28:253–255PubMedGoogle Scholar
  18. Mueller K, Nyhan WL (1982) Modulation of the behavioural effects of amphetamine in rats by clonidine. Eur J Pharmacol 83:339–342PubMedGoogle Scholar
  19. Nurse B, Russell VA, Taljaard JJF (1984) α2-and β-Adrenoceptor agonists modulate [3H]-dopamine release from rat nucleus accumbens slices: implications for research into depression. Neurochem Res 9:1231–1238PubMedGoogle Scholar
  20. Ogren SO, Archer T, Johansson C (1983) Evidence for a selective brain noradrenergic involvement in the locomotor stimulant effects of amphetamine in the rat. Neurosci Lett 43:327–331PubMedGoogle Scholar
  21. 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 34:1093–1097PubMedGoogle Scholar
  22. Pifl, ChF, Hornykiewicz O (1985) α-Noradrenergic involvement in locomotor activity. Naunyn Schmiedeberg's Arch Pharmacol [Suppl] 330:R71Google Scholar
  23. Pijnenburg AJJ, Honig WMM, Van Rossum JM (1975) Effects of antagonists upon locomotor stimulation induced by injection of dopamine and noradrenaline into the nucleus accumbens of nialamide-pretreated rats. Psychopharmacology 41:175–180Google Scholar
  24. Plaznik A, Kostowski W (1983) The interrelationship between brain noradrenergic and dopaminergic neuronal systems in regulating animal behaviour: possible clinical implications. Psychopharmacol Bull 19:5–11PubMedGoogle Scholar
  25. Pycock CJ, Donaldson I MacG, Marsden CD (1975) Circling behaviour produced by unilateral lesions in the region of the locus coeruleus in rats. Brain Res 97:317–329PubMedGoogle Scholar
  26. Reader A, Briere R, Grondin L (1987) α1- and α2-Adrenoceptor binding in cerebral cortex: competition studies with [3H]-prazosin and [3H]-idazoxan. J Neural Transm 68:79–95PubMedGoogle Scholar
  27. Roberts DCS, Zis AP, Fibiger HC (1975) Ascending catecholamine pathways and amphetamine-induced locomotor activity: importance of dopamine and apparent non-involvement of norepinephrine. Brain Res 93:441–454PubMedGoogle Scholar
  28. Scatton B, Zivkovic B, Dedek J (1980) Antidopaminergic properties of yohimbine. J Pharmacol Exp Ther 215:494–499PubMedGoogle Scholar
  29. Scatton B, Dedek J, Zivkovic B (1983) Lack of involvement of α2-adrenoceptors in the regulation of striatal dopaminergic transmission. Eur J Pharmacol 86:427–433PubMedGoogle Scholar
  30. Staton DM, Solomon PR (1984) Microinjections ofd-amphetamine into the nucleus accumbens and caudate-putamen differentially affect stereotypy and locomotion in the rat. Physiol Psychol 12:159–162Google Scholar
  31. Thomas KV, Handley SL (1978) Modulation of dexamphetamine-induced compulsive gnawing — including the possible involvement of presynaptic α-adrenoreceptors. Psychopharmacology 56:61–67PubMedGoogle Scholar
  32. Thornburg JE, Moore KE (1973) The relative importance of dopaminergic and noradrenergic neuronal systems for the stimulation of locomotor activity induced by amphetamine and other drugs. Neuropharmacology 12:853–866PubMedGoogle Scholar
  33. Van Oene JC, de Vries JB, Horn AS (1984) The effectiveness of yohimbine in blocking rat central dopamine autoreceptors in vivo. Naunyn Schmiedeberg's Arch Pharmacol 327:304–311Google Scholar
  34. Waldmeier PC, Ortmann R, Bischoff S (1982) Modulation of dopaminergic transmission by α-noradrenergic agonists and antagonists: evidence for antidopaminergic properties of some α-antagonists. Experientia 38:1168–1176PubMedGoogle Scholar
  35. 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 16:2553–2557Google Scholar
  36. Wiszniowska-Szafraniec G, Danek L, Reichenberg K, Vetulani J (1983) Facilitation by α-adrenolytics of apomorphine gnawing behaviour: depression of threshold apomorphine concentration in the striatum of the rat. Pharmacol Biochem Behav 19:19–21PubMedGoogle Scholar
  37. Zetler G (1985) Clonidine sensitises mice for apomorphine-induced stereotypic gnawing. Antagonism by neuroleptics and cholecystokinin-like peptides. Eur J Pharmacol 111:309–318PubMedGoogle Scholar

Copyright information

© Springer-Verlag 1988

Authors and Affiliations

  • Stephen L. Dickinson
    • 1
  • Brian Gadie
    • 1
  • Ian F. Tulloch
    • 1
  1. 1.Department of PharmacologyReckitt & Colman plcKingston-Upon-HullUK

Personalised recommendations