Effect of extended depot fluphenazine treatment and withdrawal on social and other behaviors ofCebus apella monkeys

Abstract

To examine whether or not prolonged exposure to a depot neuroleptic has either residual or "tardive pathological" effects on normal behavior, 38 Cebus apella monkeys were observed daily for 108 weeks. The issue of stress influencing such effects was also addressed. During weeks 25-48 half of the monkeys received 0.22 mg/kg fluphenazine decanoate, IM, every 3 weeks, with the dose increased to 0.33 mg/kg during weeks 49-72. Behavioral measures were combined to form composite behavioral variables which quantify four major aspects of behavior: self- and environment-directed behavior, affiliation, aggression, and normal locomotor activity. Mean plasma fluphenazine levels at 48 h post-injection were 0.13 (+/- 0.03) ng/ml for injections 3-8 and 0.24 (+/- 0.07) ng/ml for injections 11-16. The pre-study null hypothesis that the four major aspects of behavior would not be adversely affected by this treatment during the drug-discontinuation phase of the study (weeks 73-108) was not statistically negated. There were highly significant decreases in self- and environment-directed behaviors and affiliation during the treatment periods, implying that treatment may contribute to the negative symptoms of treated schizophrenics. Stress reduced the above effects. Aggression showed some increase during early drug discontinuation, accentuated by stress. Recovery of normal (baseline) behavioral scores began by week 7 after the last treatment. Mild (bucco-lingual) tardive dyskinesias persisted in 30% of the animals for a prolonged time.

Behavioral effects of orally administered glycine in socially housed monkeys chronically treated with phencyclidine

“…Kibos has been used in both field and laboratory studies of naturalistic primate behaviors and to evaluate their response to psychopharmacologic interventions (O'Keeffe et al 1983;Lifshitz et al 1991Lifshitz et al , 1997Linn et al 1995Linn et al , 1999. Behavioral observations were entered directly onto microcomputers by an observer looking through a one-way mirror in the wall separating each colony room from a central observation room.…”

“…In the fluphenazine study, 18 animals received depot fluphenazine for 24 weeks at 0.22 mg/kg, followed by another 24 weeks at 0.33 mg/kg. Numerous behavioral variables were compared within-group to baseline levels and across-group to data from 19 controls (Lifshitz et al 1991). Approximately 2 years after fluphenazine treatment ended, animals received an additional 18 weeks of fluphenazine treatment at 0.33 mg/kg .…”

“…The large number of variables was reduced by the creation of "composite behavioral variables" (CBVs), which are functionally related groupings of weighted BVs, with weights reciprocally proportional to BV frequency derived during an extended baseline for 40 capuchin monkeys (when each monkey received 64 daily scores for all variables over a 24-week period; Lifshitz et al 1991;. Sums of the weighted BVs are averaged to yield CBV scores.…”

“…Comparison with behavioral data from earlier studies To determine if altered locomotor scores were a byproduct of PCP's general sedative and/or ataxic effects, we compared them with data collected during earlier studies with the typical antipsychotic fluphenazine decanoate (Lifshitz et al 1991;) and with amphetamine and apomorphine (Lifshitz et al 1997). These studies used the same observation and recording techniques as in this study.…”

Reversal of phencyclidine-induced prepulse inhibition deficits by clozapine in monkeys

“…The clozapine dose was well tolerated and did not produce excess sedation or disruption of PPI. As four of the subjects had prior exposure to the typical antipsychotic fluphenazine decanoate, we noted any signs of dyskinesias or dystonias using ratings similar to those used in our previous experiments (Lifshitz et al 1991;.…”