Risperidone (R 64 766), a potent and complete LSD antagonist in drug discrimination by rats

Risperidone was studied in a 0.16 mg/kg LSD-saline drug discrimination test procedure. At doses varying from 0.0025 to 0.63 mg/kg, no LSD-like agonist effects were observed. Studies on the antagonism of the LSD-cue indicated that risperidone was able to completely block the discriminative stimulus p...

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Bibliographic Details
Published in:Psychopharmacologia 1989-01, Vol.97 (2), p.206-212
Main Authors: MEERT, T. F, DE HAES, P, JANSSEN, P. A. J
Format: Article
Language:English
Subjects:
Animals
Biological and medical sciences
Discrimination (Psychology) - drug effects
Dose-Response Relationship, Drug
Drug addictions
Generalization, Stimulus - drug effects
Isoxazoles - pharmacology
Lysergic Acid Diethylamide - antagonists & inhibitors
Male
Medical sciences
Oxazoles - pharmacology
Piperidines - pharmacology
Rats
Rats, Inbred Strains
Risperidone
Toxicology
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Summary:Risperidone was studied in a 0.16 mg/kg LSD-saline drug discrimination test procedure. At doses varying from 0.0025 to 0.63 mg/kg, no LSD-like agonist effects were observed. Studies on the antagonism of the LSD-cue indicated that risperidone was able to completely block the discriminative stimulus properties of LSD with a minimum ED50-value of 0.028 mg/kg. Risperidone was also very active over time with reference to LSD antagonism, the ED50S after 2, 4 and 8 h pretreatment being 0.028, 0.064 and 0.44 mg/kg. Response rate reductions were only observed at doses greater than or equal to 0.16 mg/kg after 1 h and at 0.63 mg/kg after 2 h pretreatment. Four and 8 h after treatment, no rate-reducing effects were apparent at doses up to 2.50 mg/kg. Thus at pretreatment intervals ranging between 2 and 8 h, complete antagonism of LSD without any rate effects was obtained. As compared to other LSD antagonists, risperidone was quantitatively better than setoperone and ritanserin and longer acting than pirenperone. Based on the pharmacological profile of risperidone and the other LSD antagonists, it was concluded that a potent central 5-HT2 and catecholamine antagonism is needed for a potent and complete antagonism of the 0.16 mg/kg LSD-cue. The potential clinical effect of risperidone in the positive and negative symptoms of schizophrenia is discussed.
ISSN:0033-3158
1432-2072
DOI:10.1007/BF00442251