Effects of LY354740, a novel glutamatergic metabotropic agonist, on nonhuman primate hypothalamic-pituitary-adrenal axis and noradrenergic function

The search for novel anxiolytics and antidepressants has focused on compounds with the potential to reduce excessive hypothalamic-pituitary-adrenal (HPA) axis activity. L-glutamate, an excitatory neurotransmitter ubiquitously present within the central nervous system, conceivably plays an important role in activating the neural sites involved in stress modulation. Deactivation of the HPA axis by glutamatergic neurotransmission modulation may represent a novel therapeutic approach. Accordingly, the acute intravenous effects of the novel metabotropic (mGlu2/3) agonist LY354740 were tested on bonnet macaques (Macaca radiata) undergoing acute infusions of yohimbine, a noradrenergic stimulant. Dependent measures were the magnitude of the increase of plasma cortisol and plasma 3-methoxy-4-hydroxyphenylglycol (MHPG) customarily elicited by yohimbine. Next, the effects of 6 weeks of chronic oral administration of LY354740 on baseline (postcapture) plasma cortisol and MHPG levels in comparison to the identical measure in untreated controls were assessed. Subjects chronically treated with LY354740 received yohimbine infusions which were compared to yohimbine infusions and saline infusions in non-LY354740-treated subjects. Preliminary evidence supports the view that acute LY354740 infusion resulted in a marked diminution of yohimbine-induced stress response, as manifest by a substantial attenuation of cortisol and MHPG response observed in comparison to the saline-treated yohimbine condition. Chronic oral administration of LY354740 led to postcapture baseline cortisol levels which were markedly reduced (approximately 50 percent) in comparison to untreated control subjects; however, there were no significant parallel differences in MHPG levels. Yohimbine infusions elicited an increase in cortisol and MHPG levels in both LY354740-treated and non-LY354740-treated subjects, in comparison to declines in cortisol values observed following vehicle infusions (group X time interaction; P<.0001). Chronic LY354740-treated subjects failed to achieve cortisol levels comparable in range to those of untreated subjects primarily because of their low baseline cortisol levels. In contrast, despite equivalent baselines, yohimbine-induced MHPG values were increased overall in the chronically treated group compared to the saline and yohimbine-alone groups. Thus, LY354740 markedly reduced the acute corticoid and noradrenergic response elicited by yohimbine infusion. Chronic administration of LY354740 appears to present a safe and effective mechanism to markedly down-modulate the HPA axis while retaining noradrenergic responsivity.     

Evidence for the Effectiveness of an Alternative Multisource Performance Rating Methodology

Despite persistent concerns as to the quality of performance information obtained from multisource performance ratings (MSPRs), little research has sought ways to improve the psychometric properties of MSPRs. Borrowing from past methodologies designed to improve performance ratings, we present a new method of presenting items in MSPRs, frame‐of‐reference scales (FORS), and test the efficacy of this method in a field and lab study. The field study used confirmatory factor analysis to compare the FORS to traditional rating scales and revealed that FORS are associated with increased variance due to dimensions, decreased overlap among dimensions, and decreased error. The laboratory study compared rating accuracy associated with FORS relative to frame‐of‐reference training (FORT) and a control group and demonstrated that FORS are associated with higher levels of accuracy than the control group and similar levels of accuracy as FORT. Implications for the design and implementation of FORS are discussed.     

Popularity, social acceptance, and aggression in adolescent peer groups: links with academic performance and school attendance

This article reports a short-term longitudinal study focusing on popularity and social acceptance as predictors of academic engagement for a sample of 342 adolescents (approximate average age of 14). These youths were followed for 4 consecutive semesters. Popularity, social acceptance, and aggression were assessed with a peer nomination inventory, and data on academic engagement were obtained from school records. For adolescents who were highly aggressive, increases in popularity were associated with increases in unexplained absences and decreases in grade point average. Conversely, changes in social acceptance were not predictive of changes in grade point average or unexplained absences. These results highlight the importance of multidimensional conceptualizations of social standing for research on school adjustment during adolescence and emphasize the potential risks associated with popularity.     

Effects of receptive language training on receptive and expressive language development

The effects of a six-month training program in receptive language on receptive and expressive language development were investigated. Developmentally retarded preschoolers were pretested and posttested on one standardized test of receptive language and two tests of expressive language. Both the training and control groups participated in a preschool program. In addition, the training group received a two-sequence training program: (1) reinforcement for matching responses to modeling cues and accompanying verbal requests, and (2) reinforcement for appropriate responses to verbal requests alone. The training group demonstrated a significant increase in appropriate responses to verbal request over base-rate performance after the training and also demonstrated a significantly improved posttest performance on one test of expressive language as compared to the control group.The authors wish to thank Mrs. Helen Huggins and the staff of the Aid to Retarded Children's Preschool Training Center, San Francisco, California, for their assistance in this study. A modified version of this paper was presented at the Gatlinburg Conference on Mental Retardation, March, 1974, Gatlinburg, Tennessee.     

Continuous Response Monitoring of Relative Time-to-Contact Judgments: Does Effective Information Change During an Approach Event?

In many previous studies of time-to-contact (TTC) judgments of approaching objects, a response was measured after observers viewed the entire event and was used to infer the informational basis for the judgment. Such measures primarily reflect the information used at the end of the approach event and may not reveal whether observers used different information at different times during the event. Evidence indicates that observers use multiple information sources and that the effectiveness of information varies with distance. We introduce a method in which observers continuously report which of 2 approaching objects would reach them first, throughout the approach. We identified the occurrence and time of response reversals. Most observers changed their relative TTC judgments during the event. The pattern of responses indicated that observers did not use tau early during the approach when objects were far and did not use optical size later when the objects were closer. Most observers relied on either optical size or optical expansion rate early during the approach and expansion rate later during the event, although there were individual differences. A single relative TTC judgment measured after observers view an approach event may not reflect judgments or their informational basis throughout the entire event.