Novel oral drug administration in an animal model of neuroleptic therapy.
A novel method of oral drug administration was used in a neuroleptic animal study. Seventy male Sprague-Dawley rats were randomly subdivided into four groups, which were treated with clozapine, haloperidol, diazepam or a vehicle solution (5% sucrose solution). Oral drug treatment was achieved by training the rats to drink the drug of choice mixed with five percent sucrose or vehicle solution from a syringe. Within 3-4 weeks the haloperidol group developed vacuous chewing movement, which did not disappear with discontinuation of the drug. Significant weight gain was observed for all drug groups in relation to the control group, whereas only the diazepam group showed a significant increase in response latency on the disengage test of sensorimotor function, which disappeared with drug withdrawal. A novel means of testing the motivational status showed that all drug-treated groups engaged in eating chocolate before grooming (t=11.69, p<0.001), whereas the control group showed no specific tendency towards either task. Furthermore, there was a significant delay in grooming for the haloperidol group compared to the other drug groups and controls. In conclusion, a novel method of oral drug administration with minimum stress was introduced that was sufficient to cause the described changes in behavioural parameters. Additionally, the combination of tests used provided an efficient discrimination between the behavioural effects of clozapine, haloperidol and diazepam in rodents.
Schleimer
Sonja B
SB
Department of Pharmacology, School of Medical Sciences, Institute for Biomedical Research and Neuroscience Institute of Schizophrenia and Allied Disorders, Blackburn Bldg. DO6, The University of Sydney, NSW 2006, Australia. sonny@med.usyd.edu.au
Johnston
Graham A R
GA
Henderson
Jasmine M
JM
D000284:Administration, Oral; D000818:Animals; D014150:Antipsychotic Agents / Q000008:administration & dosage* / Q000009:adverse effects*; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D001835:Body Weight / Q000187:drug effects / Q000502:physiology; D001921:Brain / Q000187:drug effects* / Q000503:physiopathology; D003024:Clozapine / Q000008:administration & dosage / Q000009:adverse effects; D003975:Diazepam / Q000008:administration & dosage / Q000009:adverse effects; D004195:Disease Models, Animal; D004409:Dyskinesia, Drug-Induced / Q000503:physiopathology*; D006120:Grooming / Q000187:drug effects / Q000502:physiology; D006220:Haloperidol / Q000008:administration & dosage / Q000009:adverse effects; D008297:Male; D008409:Mastication / Q000187:drug effects* / Q000502:physiology; D009042:Motivation; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects / Q000502:physiology
D014150:Antipsychotic Agents; D003024:Clozapine; D006220:Haloperidol; D003975:Diazepam