Postnatal experiences and genetic effects on squirrel monkey social affinities and emotional distress.

Most nonhuman primate research on risk factors underlying vulnerability to stress has focused on early psychosocial experiences in various species of macaques. To test for genetic and experiential effects on emotional vulnerability in randomly bred squirrel monkeys, here we combined a paternal half-sibling analysis with three postnatal rearing protocols that altered aspects of maternal availability. In one condition offspring were periodically removed from natal groups, whereas differences in maternal availability were produced in two other conditions by manipulating the effort required of lactating mothers to successfully locate food. After completion of these protocols at 21 weeks of age, social affinities, maternal separation induced peep-calls, and plasma levels of cortisol were assessed from 29 to 37 weeks of age. Significant postnatal rearing effects and the lowest heritabilities were detected in peak elevations of cortisol measured 1 day after the removal of mothers from otherwise undisturbed groups. Individual differences in cortisol 3-7 days later revealed negligible postnatal rearing effects and the highest heritabilities (h(2) approximately. 70), as offspring sired by certain fathers failed to return to the preseparation level found in undisturbed natal groups. Paternal half-siblings that responded with long lasting increases in cortisol spent more time near their mother in undisturbed groups and exhibited long-lasting increases in separation induced peep-calls. These findings concur with human twin studies that suggest genetic and experiential factors contribute to individual differences in vulnerability to emotional distress.

Salivary cortisol levels in socially phobic adolescent girls.

Anxiety disorders such as social phobia (SP) often have their onset during adolescence and frequently precede the onset of major depression. Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis is well-documented in major depression. Consequently, there is considerable interest in HPA function in anxiety disorders. We examined salivary cortisol levels in 27 SP adolescent girls and 21 matched controls during normal daily activities, and immediately before and after a modified Trier Social Stress Test (TSST). Both SP subjects and controls showed significant elevations in cortisol levels prior to the TSST, and prior to attending school. These results suggest that salivary cortisol is a sensitive measure of anticipatory anxiety, but we failed to find significant differences between SP subjects and controls.

Primate brain evolution: genetic and functional considerations.

Functionally distinct regions of the brain to which maternal and paternal genomes contribute differentially (through genomic imprinting) have developed differentially over phylogenetic time. While certain regions of the primate forebrain (neocortex, striatum) have expanded relative to the rest of the brain, other forebrain regions have contracted in size (hypothalamus, septum). Areas of relative expansion are those to which the maternal genome makes a substantial developmental contribution. This may be significant with respect to the importance of primate forebrain expansion in the development of complex behavioural strategies and the way in which these are deployed, especially by the matriline. In many primate societies the maintenance of social cohesion and group continuity over successive generations is dependent on the matriline, with high ranking females producing high ranking daughters that stay within the group. Regions of relative contraction are those to which the paternal genome makes a differential contribution and these are target areas for gonadal hormones, which is congruent with the diminished role for gonadal hormones in the emancipation of primate reproductive behaviour.

Effects of opioid receptor blockade on the social behavior of rhesus monkeys living in large family groups.

Rhesus monkeys of 9 weeks, 48 weeks, 100 weeks, 150 weeks of age (young subjects), or mature parous females that were not lactating were given acute single doses of the opioid antagonist naloxone (0.5 mg/kg) and vehicle on different days and observed in their familial social groups. Naloxone increased the occurrence of affiliative behaviours. Young subjects spent more time in contact with their mothers but showed no changes in social grooming. Maternal contact was actively sought through contact vocalizations, decreasing proximity, and, for the youngest infants, increased attempts to suckle. Mature females made more solicitations for grooming and received more grooming from their companions. These results are interpreted in terms of naloxone blocking the positive effect arising from social contact and thus causing subjects to seek further affiliative comfort.

Behavioral assessment of the effects of embryonic nigral grafts in marmosets with unilateral 6-OHDA lesions of the nigrostriatal pathway.

Grafts of embryonic nigral tissue were made into the striatum of marmosets (Callithrix jacchus) which had previously received a unilateral 6-hydroxydopamine (6-OHDA) lesion of the nigrostriatal bundle. The grafts comprised injections of cell suspensions prepared from embryonic (74 day) marmoset ventral mesencephalic tissue targeted at multiple striatal sites in the caudate nucleus, the putamen, and the nucleus accumbens on the same side as the initial lesion. A series of behavioral tests was used to assess the monkeys prior to surgery, following the 6-OHDA lesion, and at regular intervals for 6 months after transplantation surgery. Lesioned and grafted (n = 6) or lesion alone (n = 4) monkeys were matched as far as possible with respect to their scores prior to transplantation so that explicit graft-derived recovery could be distinguished from any spontaneous recovery that might occur. Sham-lesioned or unoperated monkeys served as further controls (n = 5). The grafts were functionally effective as measured by a reduction, and in some cases a reversal, of spontaneous, amphetamine- and apomorphine-induced rotation. The reversal of amphetamine-induced rotation correlated with the number of dopaminergic neurons in the grafts visualized by tyrosine hydroxylase immunohistochemistry. Successful use of the hands was restored by the grafts on tasks in which the monkeys reached into tubes to retrieve food. However, functional recovery was not seen on some other behavioral tests. In particular, grafts did not influence ipsilateral biases induced by the lesion, including the position of the head with respect to the rest of the body, hand preference while reaching for food at a conveyor belt, and neglect of contralateral stimuli either at the conveyor belt or of adhesive labels placed around the feet. Indeed, the graft group was impaired compared with the lesion group in the accuracy of reaches at the conveyor belt. Overall, these results indicate that embryonic nigral grafts can yield a partial recovery from the symptoms induced by unilateral nigrostriatal lesions in a primate model of hemiparkinsonism.

Opioid receptor blockade reduces maternal affect and social grooming in rhesus monkeys.

Seven lactating female rhesus macaques, housed in social groups, were administered with low doses (0.5 mg/kg) of the opioid antagonist naloxone when their infants were 4, 6, 8, and 10 weeks old. A control group received saline. Mothers receiving naloxone were involved in less grooming with other group members, and were less protective towards their infants. By infant-age week 8 they also groomed their infants less, while other monkeys groomed the infants more. Other behavioural measures of mother-infant interactions were not altered. With time, from infant-age week 6 onwards, some short-lived dysphoric conditioned drug responses to naloxone became apparent, although these were not correlated with the decline in social interaction. These results are interpreted in terms of possible interference of naloxone with maternal affect.

Anxiety in rhesus monkey infants in relation to interactions with their mother and other social companions.

In this study the anxiety-related components of rhesus monkey infant behavior at an early stage of social development were examined. Eight rhesus infants (age 30-40 weeks) belonging to 3 captive groups were administered with an anxiogenic drug (beta-CCE; 0.2 mg/kg) and an anxiolytic drug (midazolam; 0.2 mg/kg). Saline solution was used as placebo. All infants were tested twice with each drug (four times with placebo) and their behavioral interactions with their mother and other social companions were recorded in 1-hr observation sessions. No convulsant or sedative effects of the drugs were observed. beta-CCE was associated with an increase in time spent by the infant with its mother and a concomitant reduction in proximity with other individuals and in social play. Midazolam did not affect the mother-infant interaction but increased the infant's locomotor activity away from the mother and its proximity and social play with juveniles and subadults when compared to peers. These results suggest that, although infant anxiety can be experimentally induced, it is not a major component of the mother-infant relationship. Infant anxiety, however, might affect the formation of other social bonds and play a part in the development of avoidance responses toward other individuals.

Proactive interference effects on short-term memory in rats: I. Basic parameters and drug effects.

An operant delayed-matching task was used to assess the role of proactive interference (PI) effects on short-term memory capacity of rats. Task performance was analyzed in terms of the influence of the sample positions and response choices on previous trials. PI was predominantly attributable to the influence of the immediately previous trial but not preceding trials and was abolished by increasing the intertrial intervals from 5 to 15 s. Nicotine induced a decline in choice accuracy only on trials in which the previous response had been to the side opposite the current sample and correct response, suggesting an increased susceptibility to PI. Physostigmine induced a mild, relatively nonspecific decline in response accuracy. Clonidine induced delay-dependent impairments irrespective of responses on previous trials. None of these drugs enhanced choice accuracy at any dose tested.

Proactive interference effects on short-term memory in rats: II. Effects in young and aged rats.

Whether the short-term memory impairments of aged rats in an operant delayed-matching task is attributable to increased susceptibility to proactive interference (PI) was tested. Groups of young and aged rats were trained on the task, and the previously reported delay-dependent deficit of aged rats was replicated. The aged rats showed a significantly greater decline in performance on previous-response-opposite trials compared with previous-response-same trials than did young rats, when tested over the same range of delay intervals, suggesting a higher sensitivity to PI. However, this effect was established against a higher overall baseline performance of the young animals on both types of trial. When the young and aged animals were equated for performance on previous-response-same trials (by increasing the range of delay intervals used for testing the young animals), the interaction effect was abolished. Thus, the delay-dependent deficits of aged rats are independent of their sensitivity to PI.

Nigral grafts in neonatal rats protect from aphagia induced by subsequent adult 6-OHDA lesions: the importance of striatal location.

Previous studies have shown that dopamine-rich nigral grafts, implanted bilaterally into the intact neonatal brain, will provide some protection from the eating disorders induced by subsequent nigrostriatal 6-OHDA lesions. This has been repeated in the present study using unilaterally transplanted nigral grafts. Following adult lesions, the control animals displayed the full syndrome of aphagia, adipsia and akinesia. By contrast, 37% of the rats in the transplanted group recommenced eating following the adult lesion. Recovery was related to the size and position of the graft: protection was associated in particular with transplants located in the posterior-ventral neostriatum. The results are discussed in terms of specific patterns of graft-host interaction that may underlie protection of the regulation of eating from the loss of forebrain dopamine systems.

Factors affecting septal graft amelioration of differential reinforcement of low rates (DRL) and activity deficits after fimbria-fornix lesions.

Wound-derived trophic factors released by the injured brain are thought to reach a peak 1-2 weeks after injury. It has been proposed that such factors can promote the survival, growth and functional capacity of embryonic tissue grafts. To test the generality of this hypothesis, control rats and rats with aspirative fimbria-fornix lesions were compared with 5 groups of rats with lesions and septal grafts implanted either in the same session as the lesion or after delays from 10 days to 9 months. Animals were assessed 3 months post-transplantation on an operant differential reinforcement of low rates (DRL) task and on a test of spontaneous locomotor activity. Lesions produced impairments on all measures of DRL performance. Two graft groups showed amelioration of the DRL deficits, one graft group was unchanged, and the deficits were exacerbated in two others. There was no clear relationship between lesion-graft interval and recovery. An inverse relationship was seen, however, between recovery and the developmental age of the donor tissue. In contrast, significant recovery from lesion-induced hyperactivity was observed in the two graft groups with tissue derived from the oldest embryos. There were no clear relationships between recovery on either test, lesion-graft interval, and AChE-positive reinnervation of the host brain. The results provide further evidence that septal grafts can reverse behavioural deficits induced by fimbria-fornix lesions under some conditions, but suggest that the timing of graft surgery may not be as important a factor as donor age in this model system.