Alcoholic-like drinking in simian social groups

We have developed two protocols for inducing sustained, high-dose, alcohol-reinforced, oral alcohol drinking among some members of Macaca nemestrina social groups. Both protocols initially co-present alcohol and the entire daily food supply in a 2-h daily drinking session, with a later return to continuous availability of food. One protocol presents unflavored aqueous alcohol to partially food-deprived subjects; the other compares the drinking of flavored alcohol solutions with the drinking of equally palatable isocaloric non-alcohol solutions when monkeys are not deprived of food. Daily high-dose drinking developed in both protocols, with biomedical changes similar to those of early human alcoholism. Daily drinking to blood alcohol concentrations above 100 mg/dl was sustained in some animals after return to baseline food conditions, and this may have been related to social rank within the groups. Alcohol reinforced drinking of the flavored solutions. Although food deprivation initially produced heavier drinking, drinking with the two protocols was equivalent after return to baseline feeding conditions. These procedures open new opportunities for examining combined social and genetic influences on alcoholic-like drinking.     

Toxicology of FK506 in the cynomolgus monkey: a clinical,biochemical, and histopathological study

We investigated clinical, biochemical, and histopathological parameters in FK506-treated cynomolgus monkeys. Eight monkeys given oral FK506, 1 (n = 4) or 10 (n = 4) mg/kg daily, survived the 90 days of treatment apparently in good health and without significant changes in biochemical and histopathological parameters, as did 2 control monkeys except one monkey on 10 mg/kg/day FK506 orally, who was found to have a malignant lymphoma. In contrast, monkeys given intramuscular FK506 1 mg/kg daily (n = 4) had to be sacrificed at day 20, 25, 32, and 47 because of severe illness. They showed abnormal biochemical parameters (increased serum urea and aspartate aminotransferase activity) and major histopathological changes in the kidney (mesangial cell proliferation and acute tubular necrosis), pancreas (depletion of beta cells), liver (steatosis), and heart (cardiomyopathy). Intramuscular administration of 1 mg/kg daily resulted in serum levels ranging from 10 to 15 ng/ml, while oral administration at a dose of 1 or 10 mg/kg daily resulted in equal or even higher serum levels (range 2–70 ng/ml). Thus, the height of the serum trough level of FK506 using the enzyme immunoassay is not related to the toxicity of FK506 in cynomolgus monkeys.     

Visual cortex ablation and thresholds for successively presented stimuli in rhesus monkeys: II. Hue

Summary Rhesus monkeys were trained to discriminate successively presented hues. The smallest difference they could reliably detect was determined before and after either inferotemporal ablation, or a lesion intended to remove as much as possible of prestriate area V4 (Zeki, 1973).As a group, the animals with lesions of V4 showed good but not perfect retention of their preoperative performance, and their thresholds were unaltered. The inferotemporal group showed no retention of the simplest successive task, red versus green, but after relearning their thresholds too were unaltered. It appears that animals without inferotemporal cortex can form precise internal representations of hues, and that the basis of the inferotemporal learning impairment may depend upon the nature of the stimuli to be discriminated.     

Habituation and adaptation of the vestibuloocular reflex: a model of differential control by the vestibulocerebellum

Summary We habituated the dominant time constant of the horizontal vestibuloocular reflex (VOR) of rhesus and cynomolgus monkeys by repeated testing with steps of velocity about a vertical axis and adapted the gain of the VOR by altering visual input with magnifying and reducing lenses. After baseline values were established, the nodulus and ventral uvula of the vestibulocerebellum were ablated in two monkeys, and the effects of nodulouvulectomy and flocculectomy on VOR gain adaptation and habituation were compared. The VOR time constant decreased with repeated testing, rapidly at first and more slowly thereafter. The gain of the VOR was unaffected. Massed trials were more effective than distributed trials in producing habituation. Regardless of the schedule of testing, the VOR time constant never fell below the time constant of the semicircular canals (5 s). This finding indicates that only the slow component of the vestibular response, the component produced by velocity storage, was habituated. In agreement with this, the time constant of optokinetic after-nystagmus (OKAN) was habituated concurrently with the VOR. Average values for VOR habituation were obtained on a per session basis for six animals. The VOR gain was adapted by natural head movements in partially habituated monkeys while they wore ×2.2 magnifying or ×0.5 reducing lenses. Adaptation occurred rapidly and reached about ±30%, similar to values obtained using forced rotation. VOR gain adaptation did not cause additional habituation of the time constant. When the VOR gain was reduced in animals with a long VOR time constant, there were overshoots in eye velocity that peaked at about 6–8 s after the onset or end of constant-velocity rotation. These overshoots occurred at times when the velocity storage integrator would have been maximally activated by semicircular canal input. Since the activity generated in the canals is not altered by visual adaptation, this finding indicates that the gain element that controls rapid changes in eye velocity in the VOR is separate from that which couples afferent input to velocity storage. Nodulouvulectomy caused a prompt and permanent loss of habituation, returning VOR time constants to initial values. VOR gain adaptation, which is lost after flocculectomy, was unaffected by nodulouvulectomy. Flocculectomy did not alter habituation of the VOR or of OKAN. Using a simplified model of the VOR, the decrease in the duration of vestibular nystagmus due to habituation was related to a decrement in the dominant time constant of the velocity storage integrator (1/h ₀). Nodulouvulectomy, which reversed habituation, would be effected by decreasing h ₀, thereby increasing the VOR time constant. Small values of h ₀ would cause velocity storage to approach an ideal integrative process, leading the system to become unstable. By controlling the VOR time constant through habituation, the nodulus and uvula can stabilize the slow component of the VOR. VOR gain adaptation was related to a modification of the direct vestibular path gain g ₁, without altering the coupling to velocity storage g ₀ or its time constant (1/h ₀). The mismatched direct- and indirect-pathway gains simulated the overshoots in the dynamic response to a step in velocity, that were observed experimentally. We conclude that independent distributed elements in the VOR modify its dynamic response, under control of separate parts of the vestibulocerebellum.     

Polydipsia in the monkey generated by visual display schedules.

Discussions of adjunctive behavior still largely refer to polydipsia induced by food delivery schedules to food deprived animals. In the present experiment polydipsia was induced when socially isolated monkeys housed in barren home cages were exposed to scheduled deliveries of film and scheduled viewing of other monkeys. These data suggest the greater generality and complexity of adjunctive behaviors and show that schedule-induced polydipsia cannot be regarded as an artifact of food associated drinking.     

Nutrient composition: effects on appetite in monkeys with oral factors held constant

The effects of macronutrients on appetite and total caloric intake in monkeys (Macaca mulatta) was studied using a new feeding and infusion system which yoked intragastric infusion of various nutrients to oral ad lib intake and removed the confounding factor of palatability from the assessment of nutrient effects on feeding behavior. A suction-activated liquid diet feeding system provided free access to a nutritionally complete diet, with 1 ml of diet delivered orally by pump with each discrete suck by the monkey. A second pump was yoked to the oral feeding pump and delivered various nutrients directly into the stomach via an implanted intragastric cannula. Thus, while oral diet composition remained constant, the net diet reaching the stomach varied over ranges of 28 to 77% carbohydrate, 16 to 65% fat and 7 to 36% protein. No significant differences in total caloric intake were observed between intakes of diets with net composition of high carbohydrate or high fat. When protein was increased to 36%, total caloric intake was generally reduced, and this effect was sustained for at least 3 weeks. Therefore, protein appears to have an increased specific satiating effect beyond the caloric content, when compared to carbohydrate or fat.     

The effects of Δ9-tetrahydrocannabinol alone and in combination with cannabidiol on fixed-interval performance in rhesus monkeys

It has been reported that cannabidiol (CBD) antagonizes the effects of ⁹-tetrahydrocannabinol (THC) on operant behavior in rats and pigeons. We have replicated this finding with rhesus monkeys. Four rhesus monkeys were trained to lever press on a fixedinterval 5-min schedule of food presentation with a 1-min limited hold and 1-min time out between successive intervals. The effects of 0.3 and 1.0 mg/kg THC alone were determined three times during the experiment; before the CBD-THC interaction, after the CBD-THC interaction and once with the CBD vehicle. A dose of 30 mg/kg CBD, which alone resulted in a 24% reduction in responding, completely antagonized the response rate reduction produced by 0.3 mg/kg THC. The effects of THC revealed a rate-dependent effect that did not conform to the log-linear rate-dependency plots described for most other drugs.This research was reported at the FASEB Meeting in Atlantic City, NJ in 1978 [Fed. Proc. 37: 739 (Abs.) 1978]     

Y-maze behavior in the mouse after morphine or an enkephalin analog

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 ₂-noradrenergic antagonist yohimbine, but not by prazosin, an ₂-noradrenergic antagonist. These results suggest that clonidine-induced hyperphagia and weight gain in monkeys are mediated through ₂-noradrenergic receptors.     

Clonidine induced hyperphagia and weight gain in monkeys

The effect of the -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.To whom offprint requests should be sent     

Symmetric temporal patterns in cortical spike trains during performance of a short-term memory task

Abstract

The trion model is a highly structured representation of cortical organization_l which predicts families of symmetric spatial-temporal firing patterns inherent in cortical activity. The symmetries of these inherent firing patterns are used by the brain in short-term memory to perform higher level computations. In the present study, symmetric temporal patterns were searched for in spike trains recorded from cells in parietal cortex of a monkey performing a short-term memory task. A new method of analysis was used to map neuronal firing into sequences of integers representing relative levels of firing rate about the mean (i.e. -1, 0 and 1). The results of this analysis show families of patterns related by symmetry operations. These operations are: i. the interchanging of all the + l’s and -l’s in a given pattern sequence (CT symmetry), ii. the inverting of the temporal sequence of the mapping (T symmetry)1 and iii. the combination of the two previous operations (CT symmetry). Patterns of a given family are found across cells especially in the memory periods of the task; in most cases they reoccur within a given spike train. The pattern families predicted by the model and reported here should be further investigated in multiple microelectrode and EEG recordings. [Neural Res 1997; 19: 509-514]