Abstract
Although yohimbine has long been known to increase arousal, reactivity and anxiety in animals and humans, little is known about the behavioural effects of more selective α2-adrenoceptor antagonists such as idazoxan. In a recent experiment, however, it was found that in rats both yohimbine and idazoxan increased low rates of lever pressing, an effect also produced by amphetamine. The purpose of the present study was to investigate further the effects of yohimbine and idazoxan in comparison with those of d-amphetamine on the operant behaviour of rats. In rats trained to press a lever on a FI 60s schedule to obtain food both yohimbine and idazoxan increased response rates, although the effect of yohimbine was considerably greater than that of idazoxan. Lower doses of d-amphetamine had no consistent effect on overall rates of responding whereas a higher dose suppressed responding. Characteristically, d-amphetamine increased responding during early portions of the intervals and decreased responding during the final portions. Idazoxan and yohimbine tended to increase responding throughout the intervals except immediately after reinforcement. When idazoxan was administered in combination with prazosin FI response rates were markedly decreased. Administration of DSP4 did not alter the response rate-increasing effects of either yohimbine or idazoxan. In rats trained to discriminate d-amphetamine from saline both idazoxan and yohimbine gave rise to responding on the saline associated lever. Combination of idazoxan with d-amphetamine did not antagonise the amphetamine cue but produced substantial reductions in response rates, probably due to toxicity. These results confirm previous findings that both idazoxan and yohimbine have behavioural stimulant effects but do not clarify the mechanisms involved. It is clear, however, that the behavioural actions of these α2-adrenoceptor antagonists have little in common with those of the psychomotor stimulant amphetamine.
Similar content being viewed by others
References
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 55:111–120
Browne RG (1981) Anxiolytics antagonize yohimbine's discriminative stimulus properties. Psychopharmacology 74:245–249
Charney DS, Heninger GR, Sternberg DE (1982) Assessment of α2 adrenergic autoreceptor function in humans: effects of oral yohimbine. Life Sci 30:2033–2041
Chopin P, Pellow S, File SE (1986) The effects of yohimbine on exploratory and locomotor behaviour are attributable to its effects at noradrenaline and not at benzodiazepine receptors. Neuropharmacology 25:53–57
Clark JT, Smith ER, Davidson JM (1984) Enhancement of sexual motivation in male rats by yohimbine. Science 225:847–849
Crossley DI (1984) The effects of idazoxan, an α2-adrenoceptor antagonist, in depression — a preliminary investigation. Proc 9th Int Congr Pharmacol, Abstr 1724P
Davis M, Astrachan DI (1981) Spinal modulation of acoustic startle: opposite effects of clonidine and d-amphetamine. Psychopharmacology 75:219–225
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 241:642–650
Dettmar PW, Lynn AG, Tulloch IF (1983) Neuropharmacological studies in rodents on the action of RX 781094, a new selective α2-adrenoceptor antagonist. Neuropharmacology 6:729–737
Dickinson SL, Gadie B, Tulloch IF (1986) Differential effects of specific α-adrenoceptor antagonists on catecholamine mediated behaviour. Br J Pharmacol 89:872P
Doxey JC, Roach AG, Smith CFC (1983) Studies on RX 781094: a selective potent and specific antagonist of α2-adrenoceptors. Br J Pharmacol 78:489–505
Goldberg MR, Robertson D (1983) Yohimbine: a pharmacological probe for study of the α2-adrenoceptor. Pharmacol Rev 35:143–180
Handley SL, Thomas KV (1979) Potentiation of startle response by d-and l-amphetamine: the possible involvement of pre- and postsynaptic alpha-adrenoreceptors and other transmitter systems in the modulation of a tactile startle response. Psychopharmacology 64:105–111
Harris RA, Snell D, Loh HH (1978) Effects of stimulants, anorectics, and related drugs on schedule-controlled behavior. Psychopharmacology 56:49–55
Heffner TG, Drawbaugh RB, Zigmond MJ (1974) Amphetamine and operant behavior in rats: relationship between drug effect and control response rate. J Comp Physiol Psychol 86:1031–1043
Ho BT, Huang JT (1975) Role of dopamine in d-amphetamine discriminative responding. Pharmacol Biochem Behav 3:1085–1092
Holmberg G, Gershon S (1961) Autonomic and psychic effects of yohimbine hydrochloride. Psychopharmacologia 2:93–106
Huang M, Messing RB, Sparber SB (1987) Learning enhancement and behavioural arousal induced by yohimbine. Life Sci 41:1083–1088
Jonsson G, Hallman H, Ponzio F, Ross SB (1981) DSP4 (N-2-chloroethyl-N-ethyl-2-bromobenzylamine) — a useful denervation tool for central and peripheral noradrenaline neurones. Eur J Pharmacol 72:173–188
Katz JL (1984) Effects of clonidine and some α-adrenergic antagonists alone and in combination on schedule-controlled behavior in pigeons and mice. Psychopharmacology 83:38–43
Lambert GA, Lang WJ (1977) Interaction between yohimbine alkaloids and amphetamine in mice. Psychopharmacology 51:209–212
Langer SZ (1978) Presynaptic receptors. Nature 275:479–480
Langer SZ (1980) Presynaptic regulation of the release of catecholamines. Pharmacol Rev 32:337–362
Luttinger D, Durivage ME (1986) Alpha2-adrenergic antagonists effect on amphetamine-induced behaviors. Pharmacol Biochem Behav 25:155–160
Morley MJ, Bradshaw CM, Szabadi E (1987) DSP4 alters the effect of d-amphetamine on variable-interval performance: analysis in terms of Herrnstein's equation. Psychopharmacology 92:247–253
Pinder RM (1986) α2-Adrenoceptor antagonists as antidepressants. Drugs Future 10:841–857
Sanger DJ (1988) The α2-adrenoceptor antagonists idazoxan and yohimbine increase rates of DRL responding in rats. Psychopharmacology (in press)
Sanger DJ, Blackman DE (1976) Rate-dependent effects of drugs: a review of the literature. Pharmacol Biochem Behav 4:73–83
Sanghvi I, Gershon S (1974) Yohimbine: behavioral and biochemical effects in mice. Arch Int Pharmacodyn 210:108–120
Sara SJ (1985) The locus coeruleus and cognitive function: attempts to relate noradrenergic enhancement of signal/noise in the brain to behavior. Physiol Psychol 13:151–162
Schechter MD, Cook PG (1975) Dopaminergic mediation of the interoceptive cue produced by d-amphetamine in rats. Psychopharmacologia 42:185–193
Semerdjian-Rouquier L, Bossi L, Scatton B (1981) Determination of 5-hydroxytryptophan, serotonin and 5-hydroxyindoleacetic acid in rat and human brain and biological fluids by reversed-phase high-performance liquid chromatography with electrochemical detection. J Chromatogr 18:663–670
Sethy VH, Winter JC (1972) Effects of yohimbine and mescaline on punished behavior in the rat. Psychopharmacology 23:160–166
Snoddy AM, Tessel RE (1983) Nisoxetine and amphetamine share discriminative stimulus properties in mice. Pharmacol Biochem Behav 19:205–210
Snoddy AM, Tessel RE (1985) Prazosin: effect on psychomotor-stimulant cues and locomotor activity in mice. Eur J Pharmacol 116:221–228
Stolerman IP, D'Mello GD (1981) Role of training conditions in discrimination of central nervous system stimulants by rats. Psychopharmacology 73:295–303
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Sanger, D.J. Behavioural effects of the α2-adrenoceptor antagonists idazoxan and yohimbine in rats: comparisons with amphetamine. Psychopharmacology 96, 243–249 (1988). https://doi.org/10.1007/BF00177568
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF00177568