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PubMedDate not supplied

Behavioral effects of levonantradol and nantradol in the rhesus monkey.

In rhesus monkeys, acute administration of levonantradol and nantradol produced signs of CNS depression, including ataxia with body sag, pupil dilation, ptosis, dozing, and reduced responsivity to external stimuli. Neither compound suppressed the morphine withdrawal syndrome; however, both alleviated the chronic abdominal contraction associated with withdrawal. The directly observable effects of these compounds were not antagonized by naloxone. When levonantradol was administered every 6 hours, marked tolerance developed to both the effects of levonantradol and nabilone and THC. No signs of withdrawal were observed when levonantradol injections were abruptly discontinued. When substituted in lieu of codeine under an intravenous drug self-administration procedure, neither levonantradol nor nantradol maintained responding at rates higher than those maintained by their vehicle. Finally, the discriminative effects of levonantradol were not equivalent to those of the narcotics ethylketazocine or etorphine.

Animals↗
PubMed1990

Effect of a local ibotenic acid lesion in the visual association area on the prelunate gyrus (area V4) on saccadic reaction times in trained rhesus monkeys.

Two rhesus monkeys were trained to make saccadic eye movements from a central fixation point towards a peripheral target. Saccadic reaction times (SRTs) were measured in the gap paradigm (200 ms pause between offset of fixation point and onset of peripheral target). Target position for extensive training (SRTs of 150 to 250 saccades were collected per day) was four degrees eccentric in the lower quadrant of the visual field contralateral to the intended lesion site in area V4. For control the monkeys were also trained for target positions either in the lower quadrant ipsilateral to the intended lesion site or in the upper visual half field. After several weeks of training a bimodal distribution of saccadic reaction times, one peak at 85 ms (express saccades) and the other around 160 ms (regular saccades) was obtained for each target position. Local injection of ibotenic acid into the 4 deg representation of area V4 resulted in a unimodal distribution of saccadic reaction times (over 90% express saccades) towards the corresponding target position, leaving the distribution of reaction times for the control position unchanged. Recovery began after 5 days and was complete 8 to 10 days after the injection. From these results we conclude that V4 is involved in the generation of the longer latency peak in the distribution of saccadic reaction times by delaying the initiation of visually guided saccades.

Animals↗
PubMed1984

Effects of damage to superior colliculi and pre-tectum on movement discrimination in rhesus monkeys.

Eight rhesus monkeys (Macaca mulatta) were trained to detect an instantaneous lateral displacement of a small spot of light. The smallest movement for 79% correct performance was then determined. Severing the splenium of the corpus callosum, which has to be done to reveal the superior colliculi, had no effect on the movement threshold. But when the superior colliculi were damaged in addition, there was an initial substantial impairment in the detection of movement and a smaller but permanent elevation in the threshold. Only if the rostral superior colliculi and pretectum were spared, was there no change in threshold, and there was evidence that the pretectal rather than collicular damage may be more important in relation to movement discrimination. Tests with human observers performing the same task showed that the threshold can be elevated by imprecise fixation and accomodation, suggesting that the consequences of mid-brain damage on movement detection may be wholly or in large part attributed to oculomotor disorders.

Accommodation, Ocular↗
PubMed1989

Studies on the discriminative stimulus properties of apomorphine in rhesus monkeys.

Four rhesus monkeys were trained to discriminate the effect of apomorphine (0.1 mg/kg IM) from that of saline injections. The discriminative stimulus (DS) effect of apomorphine generalized to the dopamine D2 receptor agonist quinpirole. The D1 dopamine receptor agonist SKF 38393 elicited responses only on the saline-appropriate lever. Stimulus generalization of the dopamine autoreceptor agonist 3-PPP exhibited stereospecificity favoring the (+) over the (-) isomer. d-Amphetamine, phencyclidine, 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), and clonidine did not share the DS effect of apomorphine. The D2-selective antagonists sulpiride and metoclopramide reversed both the DS effect and the response rate reduction produced by the training dose of apomorphine. Chlorpromazine and the D1 antagonist Sch 23390 also antagonized the DS effect, but the antagonism was accompanied by a further rate reduction. Haloperidol and clozapine antagonized the DS effect incompletely. The DS effect produced by apomorphine in this study appears to be mediated predominantly by post-synaptic D2 receptor activation, with contribution also from the D1 receptor.

Animals↗
PubMedDate not supplied

Effect of polychlorinated biphenyls on several endocrine reproductive parameters in the female rhesus monkey.

Female rhesus monkeys (Macaca mulatta) ingested gelatin capsules containing daily doses of 0 (control), 5, 20, 40, or 80 micrograms of Aroclor 1254/kg/day (PCB) which was dissolved in corn oil plus glycerol. After approximately two years of dosing and when the monkeys were near an adipose tissue PCBs equilibrium, each dose group of 16 animals was randomly divided into two test groups. Daily blood samples from both groups were acquired for estrogen and progesterone analysis during one menstrual cycle. Test group 1 was sampled during February-March and test group 2 during August-September. Serum estrogen and progesterone concentrations in monkeys dosed with PCBs were equivalent to control values with the exception of the luteal phase progesterone levels in the 20 and 80 micrograms/kg/day dosed monkeys in test group 1. There was no difference in menstrual cycle length between control and treated monkeys for the month sampled, however, menses duration was marginally longer in the 80 micrograms/kg/day dose group. There were no apparent treatment related differences in the incidence of anovulatory cycles nor on the temporal relationship between the estrogen peak and menses onset, menses end or the progesterone peak.

Animals↗
PubMed1976

Pharmacokinetics of intra-amniotically administered hyperosmolar urea in rhesus monkeys.

Three rhesus monkeys in midgestation were injected intra-amniotically with hyperosmolar 14C-urea (58 per cent weight/volume, 2.3 Gm. per kilogram, 25 muc) and the concentration of 14C-urea measured serially for 24 hours in amniotic fluid, maternal serum, and maternal urine. The volume of the amniotic space was measured by isotope dilution of 99mTc-albumin. The experimental values were fitted to a three-compartment mathematical model with the aid of a digital computer program for nonlinear data. The computer-derived concentration versus time curves were in close agreement with the measured values when the flux of urea was primarily from amniotic fluid to fetal water to maternal water with insignificant direct transport between the amniotic fluid and maternal serum. The half-times for distribution of urea into fetus and mother were approximately 30 minutes and 7 hours, respectively. Thus, although the uptake of urea by the fetus from surrounding amniotic fluid is rapid, the further movement of urea from fetus to mother is relatively slow.

Abortifacient Agents↗
PubMed1980

Effect of 50 percent distal small bowel bypass on gastric secretory function in rhesus monkeys.

Six rhesus monkeys had basal acid output and histamine-stimulated maximal acid output measured before and at 10 weeks and 6 months after 50 percent distal small bowel bypass. At each stage fasting serum gastrin was measured in all animals and fasting serum gastric inhibitory polypeptide in two animals. No change in basal or maximal acid output occurred after a sham operation carried out in two of the animals. The mean preoperative basal acid output (0.17 +/- 0.02) increased to 0.49 +/- 0.04 at 10 weeks after bypass (p less than 0.001) and then decreased significantly to 0.33 +/- 0.03 mEq/kg/hour at 6 months (p less than 0.001). Preoperative maximal acid output (0.43 +/- 0.06) increased to 0.76 +/- 0.10 mEq/kg/hour at 10 weeks (p less than 0.001) and remained at that level at 6 months. Small bowel biopsy specimens at 6 months showed characteristic changes in both proximal and distal small bowel segments. Fasting gastrin and gastric inhibitory polypeptide levels did not change significantly during the study. A comparison of these results with those obtained after 50 percent distal small bowel resection in a previous study revealed a similar proportional increase in maximal acid output in both early (resection, 78 +/- 20 percent; bypass, 77 +/- 23 percent) and late postoperative studies (resection, 57 +/- 14 percent; bypass, 74 +/- 19 percent). However, the early increase in basal acid output after resection (370 +/- 50 percent) was sustained and was significantly greater (p less than 0.005) than the early ill-sustained increase (188 +/- 24 percent) after bypass.

Animals↗
PubMed1984

Subdurally recorded pattern and luminance EPs in the alert rhesus monkey.

Two rhesus monkeys (Macaca mulatta) were trained to fixate a TV screen on which checkerboard and bar patterns could be presented. Stainless steel skull electrodes and electrode bundles under the dura, each containing 7 leads permitting 7 recording sites at 5 mm intervals, were placed over the temporal-occipital cortex and used to obtain visually evoked potentials (VEPs). The following conclusions were reached: VEPs recorded with skull electrodes resemble scalp recorded VEPs. Subdural electrodes may yield larger VEP amplitudes than skull or scalp electrodes. Subdural VEPs vary more in shape with recording site than scalp or skull recorded VEPs. Apart from differences in shape there are topographical differences between luminance and pattern EPs; the luminance EP is localized near the occiput and the pattern EP is most pronounced at the temporal site overlying the foveal projection area. For a given recording site it can be seen that: (a) the amplitude of the pattern reversal EP is smaller than that of the pattern onset EP; (b) the shape of the reversal EP resembles the pattern offset EP; and (c) the shape of the pattern onset EP is rather invariant to check size and bar width. On the basis of the pattern EP the striate and prestriate cortical areas can be distinguished as follows: (a) the prestriate cortex yields a positive-negative-positive (PNP) response complex to pattern onset and the striate cortex a PN response complex; and (b) the striate cortex responds to finer patterns than the prestriate cortex.

Animals↗
PubMed1992

Visual suppression of torsional vestibular nystagmus in rhesus monkeys.

Juvenile rhesus monkeys, placed on a motorized turntable, were rotated at constant velocity and then decelerated about an Earth-vertical axis. The animals were implanted with dual search coils to measure eye movements in three dimensions. By changing the monkey's body position (upright, ear-down, supine), postrotatory nystagmus was elicited in the horizontal, vertical, or torsional direction. Peak slow phase eye velocity and time constant of velocity decay were compared between decelerations in the dark and in the light. In all nystagmus directions, illumination reduced the time constant (Tc) to values around 5 sec. Peak velocity (Vp) was markedly attenuated in the horizontal and vertical directions (around 50%), but the effect of light on Vp in the torsional direction was small (less than 20%). These findings were independent of the velocity step size. Our hypothesis is that the two dynamic components of optokinetic nystagmus, as they interact with postrotatory nystagmus during visual suppression, differ in their dimensionality: the early component (fast component, direct pathway, pursuit system) is mainly activated in the horizontal and vertical directions, while the late component (slow component, indirect pathway, optokinetic system) effectively operates in all three dimensions.

Animals↗
PubMed1983

The discriminative stimulus properties of cocaine in the rhesus monkey.

Three rhesus monkeys were trained to discriminate IM injections of cocaine (0.25 mg/kg) from saline under conditions where responding was maintained on one of two levers under a fixed-ratio 30 schedule of food delivery. The ability of other doses of cocaine and other compounds to substitute for the training dose of cocaine in controlling cocaine-appropriate responding was assessed. Cocaine (0.008-0.5 mg/kg), d-amphetamine (0.03-0.25 mg/kg) and l-cathinone (0.03-0.5 mg/kg) produced dose dependent increases in the percent of cocaine-appropriate responding in test sessions. At the highest doses tested, these three compounds produced more than 90% cocaine-appropriate responding suggesting that they share discriminative stimulus properties. When nicotine (0.125-16 mg/kg) and procaine (0.06-8.0 mg/kg) were tested, some of the monkeys responded 90% or more on the cocaine-appropriate lever; in other cases there was a trend towards generalization at lower doses but when higher doses were administered, responding was suppressed. These data suggest that these two compounds have discriminative stimulus properties which differ to some extent from cocaine. Finally, when pentobarbital (2-16 mg/kg) was administered, responding occurred on the saline-appropriate lever indicating that this drug does not share the discriminative stimulus properties of cocaine.

Alkaloids↗
PubMed1984

Effects of imipramine on separation-induced vocalizations in young rhesus monkeys.

Three Rhesus monkeys were removed from their mothers at birth and reared together in a group cage. When they were one year old they were subjected to repeated separations during which they were placed alone for 1 hour in another cage in an acoustically isolated adjacent room. The number of vocalizations and gross body movements were recorded automatically. Single injections of imipramine (3.75, 7.5 and 15 mg/kg IM) instead of decreasing tended to increase the number of vocalizations without affecting motor activity. A similar pattern was observed when imipramine (3.75 and 7.5 mg/kg IM) was administered repeatedly (2 injections/day/4 days). The failure of imipramine to decrease separation-induced vocalizations in our conditions suggests that the procedure would not be useful for testing potential antidepressants.

Animals↗
PubMed1984

Effects of pentobarbital and d-amphetamine on oral phencyclidine self-administration in rhesus monkeys.

Three rhesus monkeys self-administered phencyclidine (0.25 mg/ml) during daily 3-hr sessions. Water was also available under a concurrent fixed-ratio (FR) 16 schedule. In Experiment 1, saline or three doses of pentobarbital (2.5, 5 or 10 mg/kg) were injected 10 min before phencyclidine (and water) self-administration sessions. The 2.5 mg/kg pentobarbital dose increased phencyclidine-maintained responding, the 5 mg/kg dose produced mixed effects among the three monkeys, and the 10 mg/kg dose consistently decreased phencyclidine-maintained responding. Subsequently, a saccharin solution (0.03% wt/vol) replaced phencyclidine, and the pentobarbital pretreatment procedure was repeated. Pentobarbital produced dose-related decreases in saccharin-maintained responding. In Experiment 2, saline or three doses of d-amphetamine (0.05, 0.1 or 0.2 mg/kg) were injected 10 min before the phencyclidine self-administration sessions. The 0.05 mg/kg dose produced increases in phencyclidine-maintained responding, while the two higher doses produced dose dependent decreases in responding. When a saccharin solution (0.03%, wt/vol) replaced phencyclidine during the daily sessions, d-amphetamine produced only dose-related decreases in saccharin-maintained responding. These results indicate that pentobarbital and d-amphetamine have a biphasic effect on phencyclidine-maintained behavior; low doses increased responding and high doses decreased responding.

Animals↗
PubMed1991

Selective anorexigenic effects of corticotropin releasing hormone in the rhesus monkey.

1. Rhesus monkeys were equipped with a novel intracerebroventricular (i.c.v.) cannula system and trained to respond under operant schedules of food presentation or termination of stimuli associated with the delivery of shock (escape). 2. CRH decreased food-maintained behavior in a dose-related manner over the range of (0.3-10 micrograms/kg) but did not affect escape responding, demonstrating a selective effect on food-maintained responding. 3. This selective effect was related to the tendency for responding to stop after delivery of a food pellet when higher doses of CRH were given, consistent with the notion that a conditioned aversion to food was established in the presence of CRH. 4. This may suggest that in hyperaroused clinical states such as depression and anorexia nervosa, focus is shifted away from appetitive tasks as a result of increased levels of CRH.

Animals↗
PubMed1981

Intracerebral self-administration of amphetamine by rhesus monkeys.

Four rhesus monkeys received intracranial implantation of cannulae aimed at the orbitofrontal cortex. Electrical intracranial self-stimulation was obtained readily from insulated electrodes placed temporarily into the orbitofrontal cortex via the outer guide tubes. Subsequently, each subject acquired a panel press operant response to deliver 0.05 microliter of D-amphetamine (10-6 M) into the orbitofrontal cortex via an inner cannula. The rate of panel pressing increased over several daily test sessions and extinguished after substitution of the vehicle solution. One animal responded readily on a fixed ratio-10 schedule. Control injections into the nucleus accumbens and lateral ventricles failed to maintain self-administration behavior.

Animals↗
PubMed1980

Metabolic labelling of P. knowlesi-specific glycoproteins in membranes of parasitized rhesus monkey erythrocytes.

Rhesus monkey erythrocytes infected with P. knowlesi at high degrees of synchrony were metabolically labeled in vitro during the early schizont stage, using 14C-amino acids and 14C-glucosamine as precursors. Parasite-specific proteins in purified schizonts and host-cell membranes were characterized by their isoelectric points and molecular masses, using isoelectric focusing in polyacrylamide and dodecyl sulfate polyacrylamide gel electrophoresis, respectively. Both 14C-amino acids and 14C-glucosamine caused labelling of 60,000-90,000D proteins/glycoproteins, focusing between pH 4.5 and pH 5.2. The plasmodial parasites synthesized gangliosides and/or other glycolipids, leading to their appearance in the host cell membrane.

Amino Acids↗
PubMed1987

Self-administration of minaprine in rhesus monkeys.

Four rhesus monkeys trained to press levers for intravenous cocaine infusions were tested with saline and minaprine [3-(2-morpholinoethylamino)-4-methyl-6-phenyl pyridazine dihydrochloride, 3-300 micrograms/kg per infusion] during daily 1-h sessions. From 4 to over 25 times more cocaine infusions were obtained than saline infusions during baseline sessions. When minaprine was substituted for cocaine, none of the tested doses maintained responding above saline levels in two of the monkeys. Some doses of minaprine did maintain responding slightly above those of saline in the other two monkeys; however, the average number of infusions and the within-session time course of minaprine infusions at these doses were markedly more similar to saline than to that of cocaine. It was concluded that minaprine did not serve as a positive reinforcer under the present experimental conditions for any of the monkeys and it was predicted that minaprine would have low liability for recreational use in humans.

Animals↗
PubMedDate not supplied

Lead exposure and diet: differential effects on social development in the rhesus monkey.

Infant rhesus monkeys ingested 0 or 1.0 mg/kg lead acetate daily from birth to one year postpartum in dietary milk. Half the monkeys in each group were offered milk ad lib, and half were given restricted quantities. Chow was available ad lib to all monkeys. Groups of 4 monkeys interacted for 1.5 h/day, 5 days/week beginning at approximately 2 months of age. The social sessions were moved to a larger arena at about 9 months postpartum. Ongoing behavior was observed during social sessions twice weekly beginning at about 3 months of age for 28 weeks, and again beginning at about 16 months of age for 11 weeks. Play behaviors were particularly susceptible to lead; social play was more severely disrupted than nonsocial play. Lead suppressed play in both test environments during the first year postpartum while self-stimulation and fearful behaviors increased. Lead-associated alterations in behavior were still present several months following termination of lead intake. Restriction of milk resulted in increased chow consumption but had little impact on behavior. Effects of lead may have been more profound in monkeys maintained on the restricted milk diet than in monkeys given milk ad lib.

Animals↗
PubMedDate not supplied

Endocrine disruption and cognitive function in adolescent female rhesus monkeys.

Female rhesus monkeys (n=8/group) received daily oral doses of exogenous estrogen [diethylstilbestrol (DES), 0.5 mg/kg, methoxychlor (MXC), 25 or 50 mg/kg] for 6 months before and after the anticipated age of menarche. Behavior was assessed during and for 9 months after dosing. Visual discrimination performance (simultaneous nonmatch-to-sample with trial-unique stimuli) conducted during dosing demonstrated delayed improvement and poorer performance in the MXC50 group, with some similar effects in the DES group. Visual recognition memory, assessed with delays of < or = 3 s, was not apparently affected. Spatial working memory, assessed after dosing, also showed acquisition deficits and possible working memory difficulties in the MXC50 group. Spontaneous motor activity, monitored at 6-month intervals, was not affected by treatment. Late peak latencies of the auditory brainstem response (ABR) were shorter in the DES group 6 months after treatment, suggesting long-term effects on brain. The study suggests that some aspects of brain function can be modified by exposure to exogenous estrogen during pubertal development. Although DES is a more potent estrogen, the high-dose MXC group was more affected behaviorally. Differential effects of the two agents at the estrogen receptor subtypes (ER alpha and ER beta) may be relevant to the differential behavioral outcomes.

Animals↗