Florid psychotic episodes are treated with antipsychotic drugs (neuroleptics). Studies have shown that patients who have been maintained on these medications have a high rehospitalization rate for psychotic episodes when their medication is discontinued or reduced. Some of these psychotic episodes may be the result of changes induced by exposure to antipsychotic agents (analogous to tardive dyskinesia). This proposal suggests that it is likely that unrecognized behavioral alterations may result from exposure to antipsychotic medications. Of particular concern is the relationship between these medications and behavioral stress. Since antipsychotic medications are selected, in part, on the basis of their ability to reduce stress responsibity, there is a possibility that upon their discontinuation homeostatic mechanisms may cause an increased behavioral sensitivity to stressful conditions. The possibility that prolonged exposure to antipsychotic medication may have detrimental (and perhaps permanent) effects upon normal behavioral characteristics cannot feasibly be evaluated in subjects who have current serious behavioral problems or a history of such problems. Ethical considerations prohibit using normal human subjects to evaluate this possibility. This application addresses these issues by proposing a study of the effects of prolonged antipsychotic medication exposure on the behavior of socially living cebus monkeys (capuchins). The treated monkeys will be exposed for 51 weeks to periodic injections of fluphenazine decanoate in amounts comparable to those used in treating human subjects, resulting in blood level comparability to human data. The pre- and post-medication periods of the study will each be 30 weeks long. By means of a detailed scoring system the behavior of 16 treated and 16 untreated animals will be continuously evaluated. The composite behavioral variables (CBVs) of interest are aggressivity, affiliation, self-maintenance and motor activity. These variables will be evaluated under unstressed and behaviorally stressed conditions. CBV data, fluphenazine blood-level data, and computer-extracted electroencephalographic variables will all be studied for their prognostic usefulness in indicating detrimental changes which may occur in individual animals. The cebus monkey EEG data obtained in this study will also be used to clarify to what extent the already known changes in the EEGs of chronic schizophrenic patients are related to their prior exposure to antipsychotic medication.
| Linn, G S; Lifshitz, K; O'Keeffe, R T et al. (2001) Increased incidence of dyskinesias and other behavioral effects of re-exposure to neuroleptic treatment in social colonies of Cebus apella monkeys. Psychopharmacology (Berl) 153:285-94 |
| Lifshitz, K; O'Keeffe, R T; Linn, G S et al. (1997) Effects of dopamine agonists on Cebus apella monkeys with previous long-term exposure to fluphenazine. Biol Psychiatry 41:657-67 |
| Lifshitz, K; O'Keeffe, R T; Lee, K L et al. (1991) Effect of extended depot fluphenazine treatment and withdrawal on social and other behaviors of Cebus apella monkeys. Psychopharmacology (Berl) 105:492-500 |
