Kenneth Lifshitz

Behavioral effects of chronic phencyclidine in monkeys.

Phencyclidine (PCP) and other NMDA receptor antagonists such as ketamine induce psychotic symptoms that are difficult to reverse with current medications and which closely resemble those of schizophrenia. This study investigated the behavioral effects of continuous PCP administration in six socially-housed Cebus apella monkeys. Chronic treatment was associated with a sustained decrease in stereotyped locomotion (pacing) and a sustained increase in scanning behavior. Treatment was also associated with a modest decrease in self- and environment-directed behavior and goal-directed locomotion and an increase in affiliative behavior at lower doses. Four animals had one or more episodes of extreme motoric and physiological responses precipitated by stressful events. The results indicate that behavioral effects of chronic PCP in primates differ from those seen following acute treatments and represent an appropriate model system for new antipsychotic drug development.

Nonhuman Primates in Neurotoxicity Screening and Neurobehavioral Toxicity Studies

Nonhuman primates can be used to develop models that use complex behaviors to evaluate the toxicity of pharmaceutical and other products, Primate functional observational batteries (FOBs) can be designed to resemble those used in rodent tests, although they need not focus on simple conditioned motor responses as small mammal FOBs frequently do. Primates generally are not suitable for use in most (first-tier) neurotoxic screening tests for both practical and scientific reasons, as well as for ethical ones. With regard to practicality factors of cost, animal availability, husbandry, and housing, and observer labor intensity, all increase with the use of primates. With regard to research design, accumulating evidence indicates that primate pharmacologic responsivity is affected by social variables in such a way that group-housed animals provide more realistic (valid) models of human neurobehavioral and disease processes in general. This further complicates primate use and behavioral measurement and evaluation. Data from a long-term study of semipermanant behavioral and electrophysiologic alterations brought about by extended exposure to a psychoactive medication are presented in order to illustrate these points and to indicate how such measures can be useful, and at times indispensable, in second-tier evaluation.

Kibos: A microcomputerized system for the continuous collection and analysis of behavioral data

Abstract This paper describes the design and use of an observation and recording system in which data on behavioral patterns exhibited by socially-living primates are recorded as present or absent within recurring units of time. Behavioral observations and initial editing are carried out on-line on a microcomputer. The checklist of observed behavious is open-ended and modifiable, as required by the selection of subject species and by experimental goals. Summary statistical reports are available immediately after data entry has been completed. Further editing and organization of data files take plance when data are transferred to a large computer. The virtues of this system are its ease of use by observers who can be trained rapidly, its cost-effectiveness, and its ability to record simultaneously a larger number of behaviors than other systems usually can. Included are examples of data-analytic programs which are executed after data have been transferred to a large computer.

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

To examine whether or not prolonged exposure to a depot neuroleptic has either residual or “tardive pathological” effects onnormal behavior, 38Cebus 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) wasnot 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.

A behavioral profile for stumptail macaques (Macaca arctoides)

Behavioral observations made on a group of 15 stumptail macaques living in a seminatural environment are used to delineate an activity profile for the species which embraces numerous locomotor, self-directed, environment-directed and social behaviors. Data indicating that certain animals direct or receive particular behaviors at markedly different rates than the rest of the group are noted. The data from 39,000 10-sec observational samples are used to construct a detailed behavioral time-budget for the group. The budget takes into account the co-occurrence rates of the most frequently observed behaviors with each other and with the other behaviors recorded. The activity profile constructed in this way is compared with the results of four other studies which estimate daily behavioral rates for the species. Environmental, social group composition and sampling-technique variables are considered for their probable effects upon the behavioral rates reported in both the present and the compared studies. A detailed comparison of data from the different studies permits the estimate of a species-typical rate for each of the behavioral patterns reported and commented upon. The estimated rates, expressed as a range of values indicating the percentage of time that an average group member dedicates to various behaviors, should be valid in a wide variety of environments.

Effects of dopamine agonists on Cebus apella monkeys with previous long-term exposure to fluphenazine

Sixty-one weeks after 48 weeks of treatment with fluphenazine decanoate or placebo, 37 socially living Cebus apella monkeys were evaluated for differences in dopaminergic sensitivity by exposure to 0.75 mg/kg, i.m. of amphetamine (AMPH) (indirect agonist) and apomorphine (APOM) (direct agonist). The fluphenazine-treated animals differed (p < or = 0.05) from control animals on some hourly measures of composite behavioral variables (CBVs). Animals exposed to fluphenazine showed a greater decrease in the aggressiveness CBV and a smaller decrease in self- and environment-directed behaviors than placebo animals. CBVs for normal locomotion and directs affiliation showed no significant differences. The fluphenazine-treated group showed greater agonist induction of stereotypic behavior (p < or = 0.01), and larger decreases in prolactin response to AMPH (p < or = 0.05). Our findings indicate that following extended treatment with an antipsychotic there is increased sensitivity to dopamine, as evidenced by stereotypies and possibly hypophyseal responsiveness.