Growth and reproduction in captive tufted capuchins (Cebus apella).

We present data on weight and reproduction from a colony of tufted capuchins monkeys (Cebus apella) over a 12 year period. The data constitute a normative record for this species. Weight at birth averages 210 g, and infants gain weight rapidly. Females typically first conceived just after their fifth birthday, and males were fertile by 4 years, 5 months. Interbirth intervals average 576 days. Eighty-seven percent of live-born infants survived past 6 months. Three of eight live-born infants that died prior to 6 months succumbed from trauma inflicted by cage mates.

Developmental changes in manipulation in tufted capuchins (Cebus apella) from birth through 2 years and their relation to foraging and weaning.

This study examined the contributions of physical and sensorimotor development to manipulation in capuchins (Cebus apella) from birth to 2 years. Between months 1-6 and 7-12, manipulation increased significantly in frequency, in the proportion that was vigorous or required fine motor control, and in the proportion directed at portable objects. Fine motor control, moving objects in relation to the body, and stamina are largely in place by 12 months, after which little changed. All elements of the manipulative repertoire have appeared, and vigorous and dexterous activities have peaked before fully independent foraging. Emergence of permanent dentition and achievement of approximately half of adult body size accompany the attainment of fully independent foraging at 15 months. Thereafter, increasing strength and specific knowledge probably contribute more to changing foraging competence in young capuchins than do stamina and sensorimotor development.

Neurochemical correlates of antiepileptic drugs in the genetically epilepsy-prone rat (GEPR).

The GEPR model is composed of two independently derived strains of rats each characterized by a broad-based seizure predisposition. Moderate seizure GEPRs (GEPR-3s) exhibit generalized clonus with loss of righting reflex in response to a standardized sound stimulus. The same stimulus in severe seizure GEPRs (GEPR-9s) produces a tonic-clonic convulsion much like that produced by supramaximal electroshock. The numeric descriptors (3 and 9) derive from the ordinal rating scale developed by Jobe and coworkers for evaluation of convulsion intensity. GEPRs experience an anticonvulsant effect in response to all established and many experimental antiepileptic drugs and distinctions between the classes of drugs can be made. Since serotonin plays an anticonvulsant role in nearly all animal seizure models, we examined the effects of antiepileptic drugs on serotonin using microdialysis. Among clinically effective anticonvulsants, carbamazepine, antiepilepsirine (used in China) and loreclezole produced dose-related anticonvulsant effects and increases in extracellular serotonin in GEPRs. Similarly, drugs known to block serotonin reuptake and increase extracellular serotonin (fluoxetine and sertraline) produce dose related anticonvulsant effects in GEPRs and other animal models. Accentuation of serotonin release by treating GEPRs with fluoxetine and 5-hydroxytryptophan enhances the anticonvulsant effect produced by fluoxetine. Depletion of serotonin greatly decreased the anticonvulsant effect produced by carbamazepine, antiepilepsirine and fluoxetine. Phenytoin produced a dose related anticonvulsant effect in GEPRs but did not increase extracellular serotonin. Depletion of serotonin did not diminish the anticonvulsant effect produced by phenytoin. Thus, serotonin appears to play a role in the anticonvulsant effect of several but not all anticonvulsant drugs.

Anticonvulsant properties of D-20443 in genetically epilepsy-prone rats: prediction of clinical response.

D-20443 is an experimental antiepileptic drug. Its mechanism of antiepileptic action is unknown. We evaluated the anticonvulsant effectiveness of D-20443 against sound-induced seizures in genetically epilepsy-prone rats (GEPRs). This compound produced anticonvulsant effects against sound-induced seizures in moderate seizure GEPRs (GEPR-3s) at significantly lower doses than in severe seizure GEPRs (GEPR-9s). Based on these data and on the responses of GEPRs to other antiepileptic drugs, we predict that D-20443 will be a broad spectrum antiepileptic agent in humans. That is, we predict that D-20443 will suppress both tonic/clonic and absence seizures in humans.

The genetically epilepsy-prone rat (GEPR).

Two independently inbred strains of genetically epilepsy-prone rats (GEPRs) have been developed. GEPR-3s and GEPR-9s have moderate and severe degrees of seizure predisposition as well as expression, respectively. Seizure predisposition is a fundamental distinction between the normal and epileptic brain. Seizure predisposition in GEPRs and in humans with epilepsy includes spontaneous seizures and exaggerated seizure responsiveness and/or abnormally low thresholds to stimuli which also cause seizures in non-epileptic subjects. Activation of brainstem seizure circuitry by auditory input via the inferior colliculus causes electrographic and behavioral responses in GEPR-9s which replicates human generalized tonic/clonic seizures. Activation of brainstem seizure circuitry by input from forebrain seizure circuitry in GEPRs provides a newly discovered model of complex partial seizures with secondary generalization to tonic/clonic seizures. Thus, seizure predisposition in GEPRs offers a unique opportunity to study the human epilepsies that is not offered in studies of normal brain exposed to convulsant stimuli.

The essential role of integrative biomedical sciences in protecting and contributing to the health and well-being of our nation.

The biomedical sciences in the United States are currently experiencing the effects of an increased emphasis on in vitro models of biological and disease processes. Advances in cellular and subcellular biology have been a driving force in the funding of new research, the training of new scientists, and new drug discovery and development. The importance of new findings at the cellular and subcellular levels is not disputed. However, the corresponding decline in funding and training opportunities for biologically relevant investigations at the level of the intact animal (including humans; hereafter designated as integrative biology) is a serious threat to continued biomedical advances. The lack of resources for integrative biology has far-reaching negative consequences in 1) the development and utilization of whole animal models of disease and dysfunction; 2) assessing the relevancy of in vitro studies to physiological mechanisms; 3) the evaluation of the scientific merit of whole animal investigations and their relevancy to the nation's scientific imperatives; 4) the instruction of young scientists in the technology and especially in the methods of integrative biology, including how to develop appropriate experimental hypotheses; 5) the instruction of graduate, medical, dental, pharmacy, and nursing students in drug and disease processes in the intact human; and 6) the ability of the pharmaceutical manufacturers, the FDA, the EPA and academia to hire scientists who can develop drugs and evaluate the effects of exogenous agents on the intact animal. These negative consequences can be alleviated in a variety of ways. These include 1) increasing the availability of funding for research in integrative biology, 2) increasing the opportunities for training in integrative biology, and 3) instituting grant reviews of integrative biomedical research by peers in integrative biomedical sciences. These measures can revitalize integrative biomedical research, help ensure the continued advancement of biomedical understanding, and consequently contribute to the alleviation of human suffering.

Development of manipulation in capuchin monkeys during the first 6 months.

This study describes the orderly changes in manipulation over the first 6 months in capuchin monkeys (Cebus apella). By 6 months of age, all the basic forms of manipulation seen in adults have appeared. Actions that occur frequently in the first 8 weeks are gentle and involve sustained visual orientation and aimed reaching. Later actions are more vigorous, and involve grasping. Large increases in the rate of activity are evident over the period of development studied. The increase from the first 8 weeks to the second may be due to (a) an increase in the amount of time spent alert and active, (b) a decrease in the amount of time spent in a ventral position, (c) improvements in postural control and stamina and (d) the onset of independent locomotion. Changes in form can be attributed primarily to postural factors and to neuromuscular development (precisely aimed and controlled movements appearing in the 5th and 6th months).

Noradrenergic abnormalities in the genetically epilepsy-prone rat.

The genetically epilepsy-prone rat (GEPR) has central nervous system noradrenergic deficits as compared to normal rats. It is possible that these deficits contribute to seizure predisposition because they are exhibited by seizure-naive as well as by seizure-experienced GEPRs. On the basis of pharmacological studies, it is hypothesized that there is an inverse relation between seizure predisposition and levels of noradrenergic activity in brain. Neurochemical studies indicate that deficits exist in areas innervated by both the locus ceruleus and the lateral tegmental noradrenergic systems. These deficits exist in GEPRs without seizure experience and are more pronounced in the severe seizure strain as compared to the moderate seizure strain. We review eight experimental steps undertaken to identify more precisely the anatomical location of noradrenergic determinants of seizure predisposition. These steps illustrate the theoretical bases for the studies and describe the specific experiments completed. Evidence supports the hypothesis that noradrenergic deficits in the superior colliculus and/or ventrally adjacent regions are determinants of seizure predisposition.

Generative aspects of manipulation in tufted capuchin monkeys (Cebus apella).

Evaluating the cognitive and ontogenetic bases of tool use in primates requires comparative data on the generative nature of manipulation, including the frequency and variety of combinations of actions and objects. Thirty-one tufted capuchins (Cebus apella) of 3 age groups devoted significant proportions of time to interaction with objects and substrates. Activity that combined an object with a substrate occurred often; activities that combined 2 portable objects were less frequent. Predictions drawn from neo-Piagetian theory of an ontogenetic link between combinatorial behaviors and the onset of tool use were not supported. The frequency and generative nature of capuchins' manipulative activity, particularly acts combining objects and substrates, could account for their proclivity to use tools. The use of tools by capuchins need not involve the representational abilities proposed by neo-Piagetian theory.

Conceptual learning in capuchin monkeys.

This paper reviews concept learning in Cebus monkeys, focussing on their ability to use the identity relation, oddity and natural concepts. Capuchins are similar to other primate genera in their use of these concepts. The extant data on learning in primates generally reflect historical concerns with general processes of learning. An alternative approach which considers the tasks the animal faces in its natural environment may be better suited to the discovery of species-unique characteristics of learning. This approach has not yet been applied to Cebus.