R. Francis Schlemmer

Phencyclidine-induced stereotyped behavior in monkeys: Antagonism by pimozide☆

The psychotomimetic substance, phencyclidine (PCP), was administered chronically to selected members of a primate social colony. PCP induced stereotyped behavior in all treated monkeys at each of three test doses. Furthermore, there was a significant increase in the amount of stereotypy seen during the second and third weeks of treatment compared to the first week. The dopamine receptor blocking agent pimozide antagonized PCP stereotypy. The results are discussed in terms of dopamine mediation of these responses.

Clonidine Induced Hyperphagia and Weight Gain in Monkeys

The effect of the α-noradrenergic receptor agonist, clonidine, on food intake and weight was examined in ten adult Stumptail macaque monkeys. An intramuscular injection of 0.1 mg/kg of clonidine HCl for seven consecutive days significantly increased food intake from baseline levels throughout treatment. All but two monkeys gained weight during clonidine treatment with seven animals gaining from 5–15% of their original body weight by the end of 1 week.

Clonidine induced hyperphagia in monkeys: evidence for alpha-2 noradrenergic receptor mediation

The mechanism of clonidine-induced hyperphagia and weight gain in monkeys was studied in 11 Stumptail macaques. Clonidine induced a significant increase in food intake over baseline levels and a significant weight gain after the 3-day treatment period. Both changes induced by clonidine were antagonized by the α2-noradrenergic antagonist yohimbine, but not by prazosin, an α2-noradrenergic antagonist. These results suggest that clonidine-induced hyperphagia and weight gain in monkeys are mediated through α2-noradrenergic receptors.

Evidence for Dopamine Mediation of Submissive Gestures in the Stumptail Macaque Monkey

Evidence gathered from several experiments where stimulant drugs were given to selected members of adult Stumptail macaque social colonies is presented which suggests that dopamine systems play an important part in the mediation of submissive behavior in this species. Chronic administration of d-amphetamine, 3.2 mg/kg/day, for 12 days, induced a significant increase in submissive gestures displayed by some treated monkeys despite the lack of a significant concurrent increase in aggressive gestures directed toward these animals. This behavioral change was antagonized by haloperidol and pimozide, two agents with preferential dopamine receptor blocking properties. The dopamine receptor agonist apomorphine induced a large dose-dependent increase in submissive gestures displayed by treated monkeys. Repeated administration of apomorphine, 1.0 mg/kg/day, for 12 days, induced a significant increase in submissive gestures comparable to amphetamine in monkeys who had previously received chronic d-amphetamine treatment. In addition, it appears that the significant increase in submissive gestures by monkeys treated with the hallucinogen 5-methoxy N,N-dimethyltryptamine is also mediated through dopamine systems since the preferential dopamine receptor blockers haloperidol and trifluoperazine antagonized this response while the serotonin antagonists cinanserin, methysergide, metergoline, and cyproheptadine all failed to antagonize or even potentiate this behavioral change. These results have important implications in the study of animal behavior and may have relevance to drug-induced and endogenous psychopathologies in humans as well.

Dose-dependent behavioural changes induced by apomorphine in selected members of a primate social colony

The effect of six acute doses of the dopamine receptor agonist apomorphine on non‐human primate social and individual behaviour was studied in a social colony of four adult Stumptail macaques. Apomorphine was administered intramuscularly to 2 monkeys/day in doses ranging from 0·05 to 3·00 mg kg−1 15 min before a 1 h observation period. Apomorphine induced hyperactivity, hypervigilance, and stereotyped behaviour at doses of 0·50 mg kg−1 and greater in all 4 monkeys. In addition it also caused a dose‐dependent disruption of normal behavioural patterns. Social grooming was eliminated while the submissive gestures were significantly increased. It also induced an increase in vocalizations and suppression of food forage behaviours. The results demonstrate the role of dopamine systems in the mediation of affiliative behaviour as well as motor behaviour in a primate species. Also, since similar behavioural changes are induced in this species during chronic (+)‐amphetamine treatment, it is suggested that dopamine systems play a predominant role in amphetamineinduced behaviour in primates.

A primate model for the study of hallucinogens

An animal model for studying the actions of hallucinogenic drugs using primate social colonies is presented. Although hallucinogens induce a number of behavioral changes in this paradigm, one emergent behavior, limb jerks, appears to be selectively induced by three classes of hallucinogens in doses which correlate with those reported to be hallucinogenic in humans. Several non-hallucinogenic congeners of hallucinogens failed to significantly elicit this response. Other behavioral changes induced by hallucinogens in monkeys such as ptosis and social withdrawal may be useful in studying aspects of hallucinogen intoxication other than hallucinations, or psychosis in general. Upon daily administration, tolerance developed to all hallucinogens tested except two, as is seen in humans. Moreover, cross-tolerance between hallucinogens could be demonstrated. Further experiments with the hallucinogen 5-methoxy N,N-dimethyltryptamine revealed that although certain individual behaviors could be antagonized by serotonin antagonists, dopamine antagonists, and physostigmine, no drug completely reversed the behavioral abnormalities induced by this hallucinogen. It is suggested that this paradigm, which offers an hallucinogen-induced behavior which correlates well with the human hallucinogen response and permits observation of a wide variety of other potentially relevant behaviors in primates, may be useful in developing and testing theories of hallucinogenic drug action. It may be especially valuable in view of the present difficulties of conducting hallucinogen research in humans.

Pharmacological Probes in Primate Social Behavior

The appropriateness of interaction with other individuals constitutes a significant factor in the determination of the diagnosis and treatment response in major psychiatric categories. Therefore, animal models of these disorders which include evaluation of social behavior add an important dimension to the model. Non-human primates have been used as subjects in most social studies because of their well documented social structure and noted behavioral similarities to humans.

Absence of clonidine-induced food intake in hamsters

Previous studies support an interaction between noradrenergic and opiate systems in the control of food intake. For example, in both rats and rabbits, food intake stimulated by the noradrenergic agent clonidine is reduced by opiate antagonists. The purpose of the present study was to determine whether or not clonidine stimulated the food intake of non-food-deprived hamsters, a species which appears to lack an opiate-sensitive feeding system. Hamsters fed a chow diet did not increase their food intake when injected with clonidine in doses ranging from 0.05 to 0.25 mg/kg. Furthermore, the animals did not increase their intake of sunflower seeds, a preferred diet for hamsters.