Effects of phencyclidine and ketamine on cardiovascular activity and temperature in the squirrel monkey

Heart rate (HR), mean arterial blood pressure (BP) and core temperature (TEMP) were recorded from chair-restrained squirrel monkeys surgically prepared with chronically indwelling arterial and venous catheters to determine the effects of acute intravenous (i.v.) injections of phencyclidine and ketamine and intramuscular (i.m.) injections of ketamine. Phencyclidine (0.03-3.0 mg/kg) and ketamine (0.3-30.0 mg/kg) i.v. increased BP and decreased TEMP, and the changes in BP and in TEMP were greater in magnitude and duration after phencyclidine. Heart rate also increased monotonically after 0.03-0.3 mg/kg phencyclidine or 0.3-10.0 mg/kg ketamine, but the effects of higher doses of either drug were biphasic with decreases followed by increases in HR. When either of two doses of ketamine (10.0 and 30.0 mg/kg) was injected i.m., the effects were qualitatively similar to those observed after i.v. administration although of much less magnitude, and there was no evidence of a biphasic change in HR. The data show that these two dissociative anesthetics differ in duration of action and in magnitude of effect on cardiovascular activity and core temperature in the squirrel monkey, and that phencyclidine is approximately ten times as potent as ketamine.     

Despotic wild patas monkeys (Erythrocebus patas) in Kala Maloue, Cameroon

The socio-ecological model predicts that the quality, distribution, and patch size of food resources determines the dominance hierarchy of female monkeys based on the type of food competition they experience. Comparative studies of closely related species have evaluated the socio-ecological model and confirmed its validity. For example, female patas monkeys in Laikipia, Kenya, form a nonlinear and unstable dominance hierarchy (i.e., egalitarian), whereas females of sympatric, closely related savannah monkeys form a linear and stable dominance hierarchy (i.e., despotic), in accordance with the model's predictions of the characteristics of food resources. I compared agonistic interactions involving food between patas monkeys (Erythrocebus patas) and sympatric savannah monkeys (Cercopithecus aethiops) in Kala Maloue, Cameroon. I found linear dominance hierarchies not only in savannah monkeys, but also in patas monkeys in Kala Maloue. The rates of agonistic interactions during feeding between patas monkeys were equivalent to those between savannah monkeys in Kala Maloue; further, these rates were significantly higher than those of both Laikipia patas and savannah monkeys. The results imply that patas monkeys in Kala Maloue are not egalitarian, but are despotic, similar to savannah monkeys. Disparity in the dominance hierarchies of patas monkeys between Kala Maloue and Laikipia were attributable to the differences in the characteristics of food resources. Although patas monkeys in Laikipia subsist on small and dispersed food resources within a high-density area, those in Kala Maloue subsisted on food resources that were clumped in intermediate-sized patches within a low-density area. This study shows that the socio-ecological model is applicable not only for interspecific comparisons but also for intraspecific comparisons.     

The effects of ketamine, phencyclidine and lidocaine on catecholamine secretion from cultured bovine adrenal chromaffin cells

The ability of ketamine, phencyclidine and analogues to alter catecholamine secretion from cultured bovine adrenal chromaffin cells was investigated. Both ketamine and phencyclidine specifically inhibited nicotinic agonist-induced secretion at concentrations which did not alter secretion induced by elevated K+ depolarization. The inhibition of nicotinic agonist-induced secretion was not overcome by increasing concentrations of nicotinic agonist. The effects of stereoisomer pairs of phencyclidine-like drugs - dexoxadrol, levoxadrol and (+)PCMP, (-)PCMP - did not reveal stereospecificity for the inhibition, in contrast to the stereospecific behavioral effects of the drugs. The local anesthetic lidocaine (0.3 mM) also noncompetitively inhibited nicotinic agonist-induced secretion without inhibiting elevated K+-induced secretion. The data indicate that ketamine and phencyclidine at clinically relevant concentrations specifically inhibit the adrenal chromaffin cell nicotinic receptor at a site similar to or identical with the site of action of local anesthetic. Although the nicotinic receptor inhibition is probably not related to the anesthetic and behavioral effects of ketamine and phencyclidine, it is likely that the centrally mediated increase in sympathetic nervous system activity which is characteristic of these drugs is moderated by the peripheral blocking effects on catecholamine secretion from the adrenal medulla.     

Blood values of free-ranging patas monkeys (Erythrocebus patas)

Free-ranging patas monkeys (Erythrocebus patas) from El Guayacán island, Puerto Rico, were surveyed to establish values for the hemogram, serum biochemicals, calcium, and phosphorus. Results were tabulated for males and nonpregnant/nonlactating, pregnant, and lactating females. A summary of blood values from previous studies on captive patas monkeys was also tabulated for comparison.     

Effects of single and multiple injections of ketamine hydrochloride on serum hormone concentrations in male cynomolgus monkeys

Using simulated short- and long-term effect studies, we evaluated the effect of ketamine anesthesia on serum cortisol, testosterone, and immunoreactive luteinizing hormone (ILH) and bioactive LH (BioLH) concentrations in adult male cynomolgus monkeys. Cortisol, testosterone, and ILH were measured by use of radioimmunoassay, and BioLH was measured by use of a radioreceptor assay method. For the acute effect, the first group (eight monkeys) was given four successive intramuscular injections of ketamine (10, 5, 5, and 5 mg/kg of body weight at 0, 30, 60, and 110 min respectively). Blood samples were taken at 0, 15, 30, 45, 60, and 120 min. For the long-term effect, the second group (10 monkeys) was given a single injection of ketamine (10 mg/kg) once a week for 4 consecutive weeks. Blood samples were taken 5 to 10 min after each injection, then were used to determine the variation in hormone concentrations among the monkeys (inter-individual variation) and within each monkey (intra-individual variation). There were no statistically significant differences in serum cortisol, testosterone, ILH, and BioLH values between the first blood sample (before the ketamine injection) and sequential blood samples in monkeys of the first group. Although intra-individual variation in the hormones (i.e., hormonal change within each monkey) was not statistically significant, inter-individual variation (among the monkeys) was significantly (0.00001 < P < 0.033) different in monkeys of the second group. These results indicate that an adequate number of animals must be used to minimize animal-to-animal variability. Our results confirm that ketamine is a suitable anesthetic agent to immobilize male cynomolgus monkeys in experimental studies (short- and long-term studies) aimed at elucidating hormonal changes.     

Blood pressure and other physiological responses in awake and anesthetized guinea pigs

The effect of combinations of injectable anesthetics on mean arterial blood pressure, blood gases, heart rate and respiration of the guinea pig (NIH Outbred strain) was investigated. After a 30 minute period in which baseline resting cardiorespiratory measurements were obtained, five groups of six pigmented animals having indwelling carotid cannulas were anesthetized with (a) ketamine hydrochloride (30 mg/kg, im)/xylazine (5 mg/kg, im); (b) sodium pentobarbital (15 mg/kg, ip)/fentanyl-droperidol (0.4 mg/kg, im); (c) diazepam (5mg/kg, ip)/fentanyl citrate (0.32 mg/kg, im); (d) diazepam (5 mg/kg, ip)/alphaxalone-alphadolone acetate (45 mg/kg, im); or (e) 1% alpha-chloralose-40% urethane (0.8 ml/100g, ip). Animals were not respirated artificially and no supplemental doses of anesthetic were given. Resting blood pressure in awake animals was measured over time for as long as cannulas remained patent (109 measurements). Mean resting blood pressure, for this strain of guinea pigs, was determined to be 53.1 +/- 4.2 mmHg. There was no indication that mean arterial blood pressure changed with age in animals varying in weight from 215 g to 550 g. Under diazepam/fentanyl, blood pressure rose significantly above resting level to a mean of 71.1 +/- 6.1 mmHg. With the other four combinations, blood pressure stabilized near, but below pre-anesthesia levels (ketamine/xylazine 47.1 +/- 6.8 mmHg; pentobarbital/fentanyl-droperidol, 46.9 +/- 3.2 mmHg; diazepam/alphaxalone-alphadolone, 47.8 +/- 4.8 mmHg; chloralose-urethane, 51.0 +/- 1.2 mmHg). Under diazepam/alphaxalone-alphadolone and chloralose-urethane, respiration was depressed and blood gas levels deviated from normal to the extent that artificial ventilation would be necessary to maintain an adequate physiological state.     

Sexual harassment among captive patas monkeys (Erythrocebus patas)

Observations of the sexual harassment occurring within a captive group of patas monkeys are reported. Immature males performed most harassing attacks, while immature and adult females were infrequent harassers. The adult male of the group appeared to be the object of the majority of attacks, and on occasion the male’s copulatory behavior was modified by harassment. It is hypothesized that the harassing attacks performed by immature patas monkeys may be based upon (a) the excitatory effect of witnessing adult sexual interactions, and (b) the approach/withdraw conflict experienced during close approach to the adult male. The preservation of the one-male group structure is suggested as a possible function of sexual harassment.     

The Ketamine Analogue Methoxetamine and 3- and 4-Methoxy Analogues of Phencyclidine Are High Affinity and Selective Ligands for the Glutamate NMDA Receptor

In this paper we determined the pharmacological profiles of novel ketamine and phencyclidine analogues currently used as ‘designer drugs’ and compared them to the parent substances via the resources of the National Institute of Mental Health Psychoactive Drug Screening Program. The ketamine analogues methoxetamine ((RS)-2-(ethylamino)-2-(3-methoxyphenyl)cyclohexanone) and 3-MeO-PCE (N-ethyl-1-(3-methoxyphenyl)cyclohexanamine) and the 3- and 4-methoxy analogues of phencyclidine, (1-[1-(3-methoxyphenyl)cyclohexyl]piperidine and 1-[1-(4-methoxyphenyl)cyclohexyl]piperidine), were all high affinity ligands for the PCP-site on the glutamate NMDA receptor. In addition methoxetamine and PCP and its analogues displayed appreciable affinities for the serotonin transporter, whilst the PCP analogues exhibited high affinities for sigma receptors. Antagonism of the NMDA receptor is thought to be the key pharmacological feature underlying the actions of dissociative anaesthetics. The novel ketamine and PCP analogues had significant affinities for the NMDA receptor in radioligand binding assays, which may explain their psychotomimetic effects in human users. Additional actions on other targets could be important for delineating side-effects.     

Foraging energetics in patas monkeys (Erythrocebus patas) and tantalus monkeys (Cercopithecus aethiops tantalus): implications for reproductive seasonality

The patas monkeys (Erythrocebus patas) in Kala Maloue, Cameroon, have their birth season in the mid-dry season, whereas closely related, sympatric tantalus monkeys (Cercopithecus aethiops tantalus) have their birth season in the wet season. To evaluate the optimality of a species-specific birth season, I estimated the daily intake of available energy and gross protein, and energy expenditure for one individual of each sex of each species between respective birth and mating seasons. The monkeys obtained a larger amount of available energy and gross protein in the birth season than in the mating season. No significant seasonal differences in energy expenditure between the birth and mating season were found. Thus, the birth season appears to be timed to the season when the monkeys can obtain more surplus energy and protein. Interspecific differences in the optimality of birth season were attributed to widely exploitative foraging, supported by the patas' high locomotive ability, which may enable them to obtain more energy from seeds of Acacia seyal and gums of A. sieberiana, and more protein from grasshoppers and seeds of A. seyal in the mid-dry season than the tantalus monkeys. A review of preceding studies suggests that the availability of seeds of Acacia fruiting during the dry season may exert the dominant influence on timing of birth not only in patas but also in savanna monkeys (Cercopithecus aethiops), which include the tantalus monkeys.     

Spontaneous preeclamptic toxemia of pregnancy in the patas monkey (Erythrocebus patas).

A disease characterized by edema, proteinuria, hypoproteinemia and hypertension was seen in late gestation in patas monkeys. The initial sign was edema of the perineum, ankles and lower trunk. The onset was abrupt, occurring 7 days or less prepartum. The affected animals were not depressed, and convulsions were not seen. In 6 of the 98 pregnancies during a 1-year period, symptoms of the disease were present. The highest incidence was manifested by primiparous animals with 3 of 36 pregnancies affected. Two of 38 second pregnancies and 1 of 24 third pregnancies were also affected. Five of the animals recovered spontaneously and were normal 14 days postpartum. Edema persisted for 30 days in one female. This animal continued to be hypertensive and had persistent mild proteinuria and hypoproteinemia. She was killed approximately 1 year postpartum due to severe renal disease. The spontaneous disease seen in patas monkeys resembled toxemia of pregnancy in humans more closely than the experimentally induced disease in other animals.     

Distribution and abundance of patas monkeys (Erythrocebus patas) in Laikipia, Kenya, 1979-2004

Patas monkeys may be especially vulnerable to local extinction because they live in relatively small, female-philopatric groups at low densities and are strongly polygynous. We assessed a patas monkey population in Kenya's 9,700 km(2) Laikipia District over 25 years, using data collected in 1979-1981 and 1992-2004. The data were based on intensive observations of three study groups, "on the ground" counts, and surveys of Laikipia residents. In 1979-1981, a minimum of 415 patas monkeys lived in 14-15 groups. By 2000, the best estimate suggested 310-445 patas monkeys living in 13-17 groups over a greater surveyed area, suggesting that patas monkeys in Laikipia may have undergone a slight decline in numbers over time. Their distribution, however, was similar over time. The relative stability of this population has likely been the result of beneficial co-existence with large-scale cattle ranching. Outside Laikipia, substantial habitat alteration from rising human populations has coincided with the near disappearance of patas monkeys where they were previously more numerous. The small population in Laikipia, probably the largest remaining in Kenya, may therefore be critical to the continued existence of patas monkeys in that country and may be dependent on maintenance of large-scale ranches. Such land use provides patas monkeys with water and broad expanses of Acacia drepanolobium woodlands, the habitat to which patas are restricted in Laikipia.     

Comparison of responses to alarm calls by patas (Erythrocebus patas) and vervet (Cercopithecus aethiops) monkeys in relation to habitat structure

We studied responses to alarm calls of sympatric patas (Erythrocebus patas) and vervet (Cercopithecus aethiops) monkeys in relation to habitat structure, with the intention of understanding the relationship between the environment and predator avoidance. Patas and vervet monkeys are phylogenetically closely related and overlap in body size. However, while patas monkeys are restricted to nonriverine habitats at our study site, vervets use both nonriverine and riverine habitats, allowing us to "vary" habitat structure while controlling for effects of group size, composition, and phylogeny. Patas monkeys in the nonriverine habitat responded to mammalian predator alarm calls with a greater variety of responses than did vervets in the riverine habitat, but not when compared with vervets in the nonriverine habitat. Ecological measurements confirm subjective assessments that trees in the riverine habitat are significantly taller and occur at lower densities than trees in the nonriverine habitat. Despite the lower density of trees in the riverine habitat, locomotor behavior of focal animals indicates that canopy cover is significantly greater in the riverine than the nonriverine habitat. Differences in responses to alarm calls by the same groups of vervets in different habitat types, and convergence of vervets with patas in the same habitat type, suggest that habitat type can be a significant source of variation in antipredator behavior of primates.     

Passive joint mobility in patas monkeys (Erythrocebus patas): rehabilitation of caged animals after release into a free-ranging environment

A previous study of passive joint mobility in patas monkeys (Erythrocebus patas) showed that laboratory-caged animals had significantly greater mobility in most joints than age/sex matched free-ranging monkeys. Passive joint mobility on 27 of the same animals was measured 6 months after the caged animals were released onto a 40-hectare island. The results show that within 6 months of becoming free-ranging, typical passive joint mobility is restored. Thus, although caging directly affects measurements of morphologically-determined features in patas monkeys, confinement itself does not necessarily prevent rehabilitation if the immature monkeys are released into a free-ranging environment.     

Phencyclidine-induced depressions of cerebellar purkinje neurons

Local administration of phencyclidine (PCP) by pressure ejection elicited a dose-dependent slowing of the spontaneous discharge of cerebellar Purkinje neurons. Ketamine also depressed firing and was much less potent than PCP. Effects of both PCP and ketamine were antagonized by local or parenteral administration of antipsychotic drugs. The similarities between the electrophysiological and behavioral actions of phencyclidine suggest that alterations in neuronal discharge may underlie its psychotomimetic properties.     

Patterns of mating among male patas monkeys (Erythrocebus patas) in Kenya

An habituated group of wild patas monkeys was observed in Kenya for 550 h in 1984. Observations were made primarily during an interval that, as previous studies at the same site had demonstrated, coincided with the annual mating and conception periods. Earlier field studies of patas at other sites had reported that heterosexual patas groups had only a single resident adult male and that mating was harem-polygynous. At the Kenya site, by contrast, as many as six males were simultaneously resident and mated in the group during the conception period. Males adopted a variety of tactics to gain access to receptive females, ranging from opportunistic mating to attempts at sequestration that resembled consort behavior in other cercopithecoids such as savanna baboons and rhesus macaques. Aggressive competition for access to females took place among the males, although the number of completed copulations per male did not bear a positive relation to agonistic dominance rank. For patas monkeys, harem polygyny is only one available option within an overall mating system that is best described as a form of promiscuous polygyny, especially during periods when conception is most likely.     

Is Metaphit a phencyclidine antagonist? Studies with ketamine, phencyclidine and N-methylaspartate

The dissociative anaesthetics, phencyclidine and ketamine, block excitation of central neurones by N-methylaspartate. Using the technique of microelectrophoresis on rat spinal neurones in vivo Metaphit, a phencyclidine receptor acylating agent, was tested to see whether it would antagonise this effect of dissociative anaesthetics. The predominant effect of Metaphit was, however, to reduce N-methylaspartate induced excitation. It is concluded that Metaphit has mixed agonist/antagonist effects at the phencyclidine receptor.     

Naturally occurring Yersinia enterocolitica septicemia in patas monkeys (Erythrocebus patas)

Two cases of Yersinia enterocolitica septicemia occurred in a breeding group of 22 adult patas monkeys (Erythrocebus patas). Affected animals had acute clinical signs of depression, weakness, dehydration, hypothermia, hepatomegaly and pronounced leukopenia. Both animals died a few hours after treatment was initiated. Gross necropsy findings included jaundice, fluid in body cavities, hepatomegaly, splenomegaly, multiple white foci within the liver and spleen, generalized lymph node enlargement and numerous mucosal ulcerations in the colon. Primary histopathological lesions were multifocal hepatic necrosis, splenic necrosis, chronic ulcerative enteritis and diaphragmatic myositis with necrosis and edema. Yersinia enterocolitica was cultured from the liver, spleen, lung, jejunum and rectum. Wild rodents, particularly mice, may have been a source of infection for these animals, as the monkeys were housed in a rural, indoor-outdoor facility. A preliminary culture survey showed that some clinically normal patas monkeys harbored the organism in their intestinal tracts.     

Campylobacter jejuni isolated from patas monkeys with diarrhea

Campylobacter jejuni was isolated from 11 (46%) of 24 patas monkeys with chronic diarrhea. Eight of these 11 (73%) monkey were characterized clinically by mucohemorrhagic diarrhea for periods up to a month followed by loose, semi-formed feces for a 12-month period. Half of the monkeys were treated with erythromycin for 10 days and the other half with tetracycline for 10 days, with all responding to treatment. Despite treatment, all monkeys again had an outbreak of mucohemorrhagic diarrhea. Biopsy specimens were taken from all eight monkeys over a period of 3 months. The clinical signs, treatment, and the gross and microscopic lesions seen in these monkeys were similar to those reported in humans and animals infected with Campylobacter jejuni.     

Antagonism of caerulein, a CCK-8 receptor agonist, to the behavioral effects of ketamine in mice and rats

It has been established in experiments on male mice and rats that caerulein antagonized the behavioural effects of ketamine, an agonist of phencyclidine receptors. Caerulein (75-375 micrograms/kg) and haloperidol (0.1-1.5 mg/kg) suppressed the stereotyped behaviour and motor excitation induced by ketamine (30 mg/kg) in mice. Caerulein and haloperidol failed to affect ketamine-induced ataxia. Caerulein (10 micrograms/kg) and the opioid antagonist naloxone (5 mg/kg) completely blocked the amnestic action of ketamine (30 mg/kg) in passive avoidance experiments on rats. It seems likely that the suppression of the behavioural effects of ketamine by caerulein is related to its functional antagonism with dopamine and opioid receptors.