The therapeutic efficacy and reduction in side effects claimed for new antischizophrenic drugs such as clozapine and risperidone have been ascribed to their heightened affinity for serotonin 5-HT2 receptors rather than D-2 receptors. A case for α2-adrenoreceptor antagonism has recently been argued. We have confirmed that at least one atypical property of risperidone (a rapid decrement in its ability to depress self-stimulation) can be partly prevented by an α2-adrenoreceptor agonist (clonidine) but not by a 5-HT 2 receptor agonist (DOI). This result supports the suggested role of α 2-adrenoreceptor antagonism in counteracting extrapyramidal effects during treatment with risperidone.
Franklin K B J, Herberg L.J. (1977) Presynaptic α-adrenoreceptor receptors: the depression of self-stimulation by clonidine and its restoration by piperoxane but not by phentolamine or phenoxybenzamine. Eur J Pharmacol43: 33-38
2.
Grottick A.J., Montgomery A M J, Rose I.C., Herberg L.J. (1994) 5-HT vs DA in the behavioural effects of risperidone . Abstract of the 5th Meeting of the European Behavioural Pharmacology Society, Berlin, September 1994. Behav Pharmacol 5: Suppl 1.
3.
Herberg L.J., Stephens D N, K B J (1976) Catecholamines and self-stimulation : evidence suggesting a reinforcing role for noradrenaline and a motivating role for dopamine. Pharmacol Biochem Behav4: 575-582
4.
Leysen J.E., Janssen P M F, Schotte A., Luyten W H M L, Megens A A H P (1993) Interaction of antipsychotic drugs with neurotransmitter receptor sites in vitro and in vivo in relation to pharmacological and clinical effects: role of 5HT2 receptors. Psychopharmacology112: S40-S54
5.
Liebman J.M. (1983) Discriminating between reward and performance: a critical review of intracranial self-stimulation methodology. Neurosci Biobehav Rev7: 45-72
6.
Litman R.E., Hong W.W., Weissman E.M., Su T.P., Poter W.Z., Pickar D. (1993) Idazoxan, an α2 antagonist, augments fluphenazine in schizophrenic patients: a pilot study. J. Clin Psychopharmacol13: 264-267
7.
Megens A A H P, Awouters F H L, Schotte A., Meert T.F., Dugovic C., Niemegeers C J E, Leysen J.E. (1994) Survey on the pharmacodynamics of the new antipsychotic risperidone. Psychopharmacology114: 9-21
8.
Meltzer H.Y. (1992) The importance of serotonin dopamine interactions in the action of clozapine. Br J Psychiatr160: 22-29
9.
Nutt D.J. (1994) Putting the 'A' in atypical: does α2-adrenoceptor antagonism account for the therapeutic advantage of new antipsychotics? J Psychopharmacol8: 193-195
10.
Sahakian B.J., Hodges J. (1994) Idazoxan improves cognitive function in frontal lobe dementia. J Neurol Neurosurg Psychiatr57: 120-121
11.
Sanger D.J. (1986) Response decrement patterns after neuroleptic and non-neuroleptic drugs. Psychopharmacology89: 98-104
12.
Schaefer G.J., Michael R.P. (1992) Schedule-controlled brain self-stimulation ; has it utility for behavioral pharmacology? Neurosci Biobehav Rev16: 569-583
13.
Sumiyoshi T., Kido H., Sakamoto H., Urasaki K., Suzuki K., Yamaguchi N., Mori H., Shiba K., Yokogawa K. (1994) In vivo dopamine-D2 and serotonin-5-HT 2 receptor binding study of risperidone and haloperidol. Pharmacol Biochem Behav47: 553-557
14.
van Kammen D.P., Peters J., Yao J., van Kammen W.B., Neylan T., Shaw D., Linnoila M. (1990) Norepinephrine in acute exacerbations of chronic schizophrenia. Arch Gen Psychiatr47: 161-170
15.
Wauquier A. (1970) Neuroleptics and brain self-stimulation. Int Rev Neurobiol21: 335-403
