Neuroleptic-induced vacuous chewing movements in rodents: incidence and effects of long-term increases in haloperidol dose.
Rats treated chronically with neuroleptics develop vacuous chewing movements (VCMs), similar in some respects to tardive dyskinesia (TD) in man. The VCM syndrome was used as a model of TD to examine the ability of increased neuroleptic doses to produce long-term suppression of dyskinetic movements. The incidence and persistence of the VCM syndrome in individual rats were also assessed to look for affected and unaffected subgroups. Rats were initially treated for 15 weeks and haloperidol decanoate. For the next 21 weeks, half the group received a 50-150% increase in dose while the other half continued to receive the same dose. Animals were also followed during a 28-week withdrawal period. Total VCM ratings showed a skewed distribution, with some rats exhibiting few movements while others developed marked and persistent movements. Increasing doses did not suppress VCMs, nor did they exacerbate movements during the withdrawal period. To the extent that the VCM syndrome models TD, the absence of long-term suppression of the VCM syndrome suggests that, at this dosage range, increasing depot neuroleptic doses may not be a useful long-term strategy for TD suppression.
Egan
M F
MF
Neuropsychiatry Branch, National Institute of Mental Health, NIMH Neuroscience Research Center at St. Elizabeths, Washington, DC 20032, USA.
Hyde
T M
TM
Kleinman
J E
JE
Wyatt
R J
RJ
D000818:Animals; D003692:Delayed-Action Preparations; D004305:Dose-Response Relationship, Drug; D004409:Dyskinesia, Drug-Induced / Q000453:epidemiology / Q000523:psychology*; D006220:Haloperidol / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013375:Substance Withdrawal Syndrome / Q000523:psychology
D003692:Delayed-Action Preparations; D006220:Haloperidol