Behavioural effects of chronic haloperidol and risperidone treatment in rats

• Published in: Behavioural brain research Vol. 171; no. 2; pp. 286 - 294
• Main Authors: Karl, Tim, Duffy, Liesl, O’Brien, Elizabeth, Matsumoto, Izuru, Dedova, Irina
• Format: Journal Article
• Language: English
• Published: Shannon Elsevier B.V 10-08-2006; Elsevier Science
• Subjects: Animals; Antipsychotic Agents - administration & dosage; Antipsychotic Agents - adverse effects; Antipsychotic drug; Anxiety; Basal Ganglia Diseases - chemically induced; Biological and medical sciences; Disease Models, Animal; Dopamine Antagonists - administration & dosage; Dopamine Antagonists - adverse effects; Drug Administration Schedule; Dyskinesia, Drug-Induced - physiopathology; Exploration; Exploratory Behavior - drug effects; Extrapyramidal symptoms; Haloperidol; Haloperidol - administration & dosage; Haloperidol - adverse effects; Infusion Pumps, Implantable; Learning and memory; Male; Medical sciences; Motor activity; Motor Activity - drug effects; Neuropharmacology; Osmotic pump; Pharmacology. Drug treatments; Phenotype; Psycholeptics: tranquillizer, neuroleptic; Psychology. Psychoanalysis. Psychiatry; Psychopharmacology; Rats; Rats, Sprague-Dawley; Risperidone; Risperidone - administration & dosage; Risperidone - adverse effects; Sprague-Dawley rat; Sprague-Dawley rat; Learning and memory; Extrapyramidal symptoms; Motor activity; Exploration; Anxiety; Haloperidol; Risperidone; Antipsychotic drug; Osmotic pump; Affect affectivity; Animal model; Atypical antipsychotic; Neuroleptic; Psychotropic; Memory; Rattus norvegicus; Serotonine receptor; Learning; Acquisition process; Behavior; Nervous system diseases; Dopamine antagonist; Serotonin antagonist; Rodentia; Butyrophenone derivatives; Cerebral disorder; Symptomatology; Vertebrata; Chemotherapy; Chronic; Mammalia; D2 Dopamine receptor; Treatment; Central nervous system disease; Extrapyramidal syndrome
• ISSN: 0166-4328; 1872-7549
• DOI: 10.1016/j.bbr.2006.04.004

The therapeutic properties of typical antipsychotic drugs (APDs) such as haloperidol in schizophrenia treatment are mainly associated with their ability to block dopamine D2 receptors. This blockade is accompanied by side effects such as extrapyramidal symptoms (EPS). Atypical APDs such as risperidone have superior therapeutic efficacy possibly due to their activity at multiple receptors (in particular 5-HT2A receptors). Although the risk of EPS is significantly lower in atypical than in typical APDs, it is not negligible. To investigate and compare the behavioural profile and EPS-asssociated side effects of haloperidol and risperidone APD treatment we applied a multi-tiered, comprehensive behavioural phenotyping approach. Sprague-Dawley rats were treated chronically (28 days) with supratherapeutic EPS-inducing doses of haloperidol and risperidone using osmotic minipumps. Domains such as motor activity, exploration, memory, and anxiety were analysed together with EPS assessment (“early onset” vacuous chewing movements and catalepsy). Both APDs produced diminished motor activity and exploration, impaired working memory performances, and increased anxiety levels. These effects were more pronounced in haloperidol-treated animals. Chronic APD treatment also caused a time-course dependent elevation of EPS-like symptoms. Risperidone-treated animals showed a catalepsy-like phenotype, which differed to that of haloperidol-treated rats, indicating that processes other than the anticipated dopaminergic mechanisms are underlying this phenomenon. These EPS-related phenotypes are consistent with reported EPS-inducing D2 receptor occupancies of around 80%. Differences in the behavioural profile of haloperidol and risperidone, which were revealed by a comprehensive phenotyping strategy, are likely due to the unique receptor activation profiles of these APDs.