A stereological study of substantia nigra in young and old rhesus monkeys

The number of pigmented and non-pigmented neurons in the substantia nigra (SN) of 10 old and six young female Macaca mulatta monkeys and in three old alpha male monkeys were estimated using new stereological cell counting methods. No systematic right-left differences were noted, nor were old animals different from young ones with respect to SN volume (68.9 mm3 vs. 62.8 mm3) or absolute number of nerve cells (320,000 vs. 312,000). However, the total number of pigmented neurons was about eight times higher in old animals compared with young ones (166,000 vs. 21,400) while the total number of non-pigmented SN neurons was less than half in old animals compared with young ones (139,000 vs. 285,000). These differences create difficulties in generalizing experimental results from the rhesus animal model to man. It seems unlikely that a simple correlation can be made between pigmented and tyrosine hydroxylase (TH) positive neurons in SN in monkeys. Instead of estimating the total number of pigmented and non-pigmented cells, only SN neurons positive for TH using immunohistochemical techniques might be used an indicator of the total number of dopaminergic neurons in SN in monkeys.     

Chronic l-alpha acetylmethadol in rhesus monkeys: discriminative stimulus and other behavioral measures of dependence and withdrawal

This study characterized discriminative stimulus and other effects of naltrexone in rhesus monkeys treated daily with the long-acting opioid l-alpha acetylmethadol (LAAM). An initial dose-finding study assessed the rate-decreasing effects of naltrexone in three monkeys receiving LAAM daily (0.32-1.78 mg/kg); subsequently, these monkeys and a fourth received 1.0 mg/kg/12 hr of LAAM although discriminating between naltrexone and saline. Responding occurred on the saline lever after the administration of LAAM, whereas >90% drug-lever responding occurred after the administration of 0.1 mg/kg of naltrexone that also elicited signs of withdrawal. Naloxone and quadazocine, but not morphine, nalbuphine or ketamine, substituted for naltrexone. Morphine and nalbuphine shifted the naltrexone dose-effect curve to the right. Compared to precipitated withdrawal, deprivation-induced withdrawal occasioned less naltrexone-lever responding and fewer observable signs of withdrawal. Maximal naltrexone-level responding occurred 24 to 48 hr after the discontinuation of LAAM treatment; the frequency of other withdrawal signs also peaked 24 to 48 hr after the discontinuation of LAAM. Partial naltrexone-lever responding occurred for up to 10 days after discontinuation of LAAM treatment; 4 and 8 days after the discontinuation of LAAM treatment, 0.1 mg/kg of naltrexone did no further increase naltrexone-lever responding or withdrawal signs suggesting that less-then-maximal naltrexone-lever responding was not due to long-lasting effects of LAAM or its metabolites. The discriminative stimuli that are associated with LAAM deprivation might be different from the stimuli associated with either training condition. This study is the first antagonist discrimination in non-humans primates treated chronically with LAAM and the results indicate that the naltrexone stimulus is related to opioid withdrawal.     

Smoked heroin self-administration in rhesus monkeys

The Symphysis Pubis (SP) joint was investigated by X-ray in 96 adults without any history of disease of the joints. We evaluated the width of this joint by measuring the distance between the two articular surface at three points. We calculated the mean for the three interpubic distances and carried out statistical analysis so as to evaluate if there is a significative difference between the four age classes (< 50; 50-59; 60-69; > 70) and between males and females. We did not found statistically-significative differences between males and females, and between the age classes; nevertheless, it is to be noted that a slight widening of the SP joint can be seen in the elderly, which is thus not significant. We also noted that the medium part of the SP joint undergoes a larger widening in older people: this is probably due to degenerative changes in the fibrocartilagineous disc and the ligaments.     

Metabolic disturbances in Plasmodium coatneyi-infected rhesus monkeys

To investigate metabolic disturbances in an animal model of human malaria, four rhesus monkeys (Macaca mulatta) were infected with Plasmodium coatneyi, a parasite which induces cytoadherence of infected erythrocytes. When moribund or the parasitaemia had plateaued, the monkeys were sacrificed (3 animals) or treated with chloroquine (1 animal). Blood and cerebrospinal fluid (CSF) were sampled at intervals between inoculation and sacrifice or treatment. Arterial and CSF glucose and lactate rose during infection, indicating evolving insulin resistance. The arteriovenous difference in glucose concentration also increased, consistent with increased glucose consumption by parasitised tissues. Arterial plasma lactate rose but a positive arteriovenous concentration difference suggested tissue lactate uptake. The animal with the highest plasma lactate at sacrifice remained hyperglycaemic but also had the highest CSF lactate, the greatest cerebral sequestration and neurological depression, and biochemical and histological evidence of severe hepatic pathology. Serum cholesterol and corrected serum calcium fell consistently during infection; serum phosphate was also reduced in animals without renal impairment. These preliminary results indicate that lactic acidosis is a late complication of severe malaria and, by implication from this and other studies, hypoglycaemia occurs even later; other metabolic changes during P. coatneyi infection in rhesus monkeys also parallel those of severe falciparum malaria in humans. The model could be used in further studies of malaria-associated metabolic dysfunction and its management.     

Long-term cognitive impairment in MPTP-treated rhesus monkeys

Following MPTP administration, monkeys manifest cognitive deficits on tasks known to assess the fronto-striatal system; there are, however, no data regarding long-term cognitive effects. In this study, we examined the cognitive abilities of monkeys 10 years after MPTP administration. MPTP-treated monkeys and age-matched controls performed a spatial delayed response task with fixed and random delays. The MPTP-treated monkeys were impaired in both versions of the task. Both groups performed at the same level at very short delays suggesting that the nature of the impairment is related to a spatial memory deficit that is still apparent 10 years after treatment. These results suggest that, like Parkinson's patients, the MPTP-treated primates display spatial deficits.     

Seasonal testicular function in male rhesus monkeys

Some studies report seasonal patterns of testicular function in male rhesus monkeys even when they are housed away from females, while others suggest that exposure to sexually active females is essential for male seasonality. We conducted the present experiment (1) to test claims that seasonal testicular activation occurs in the absence of females and (2) to determine whether regular exposure to and copulation with females enhances, or is without effect upon, seasonal increases in testicular function. We studied two groups of male monkeys housed in a colony room containing no females. Males in the Female Exposure group (n = 7) were paired twice weekly with estradiol-implanted females and copulated vigorously. Males in the second group (n = 7) were placed in the same test chamber (at least 16 h after it had been scrubbed with disinfectant) but were never exposed to females. Serum testosterone levels and testis volume were monitored for both groups. Each group displayed a seasonal pattern of testosterone and of testis volume comparable in timing and magnitude to seasonal increases previously reported in group-housed males, but the two groups did not differ from each other. Our findings confirm that seasonal changes in testosterone and testis size occur in the absence of sexual interaction and demonstrate that moderate levels of sexual activity do not enhance this response.     

Music perception and octave generalization in rhesus monkeys.

Two rhesus monkeys were tested for octave generalization in 8 experiments by transposing 6- and 7-note musical passages by an octave and requiring same or different judgments. The monkeys showed no octave generalization to random-synthetic melodies, atonal melodies, or individual notes. They did show complete octave generalization to childhood songs (e.g., "Happy Birthday") and tonal melodies (from a tonality algorithm). Octave generalization was equally strong for 2-octave transpositions but not for 0.5 or 1.5-octave transpositions of childhood songs. These results combine to show that tonal melodies form musical gestalts for monkeys, as they do for humans, and retain their identity when transposed with whole octaves so that chroma (key) is preserved. This conclusion implicates similar transduction, storage, processing, and relational memory of musical passages in monkeys and humans and has implications for nature–nurture origins of music perception. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Frustration and self-aggression in social isolate rhesus monkeys.

Compared the frequency of self-aggressive behavior emitted by 6 partial social isolate and 6 socialized rhesus monkeys under baseline living conditions and a continuous reinforcement-extinction schedule of leverpressing. Under baseline conditions, male isolates showed higher levels of self-aggressive behavior than did the female isolates. Further, frustration produced by extinction of the leverpressing response produced a significant but transitory intensification of self-aggressive behavior. (16 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Sex differences in physical dependence on orally self-administered phencyclidine (PCP) in rhesus monkeys (Macaca mulatta).

Withdrawal from orally self-administered phencyclidine (PCP) has been shown to alter operant baselines of food-maintained responding. The goal of the present study was to determine whether there are sex differences in these alterations. Seven female and 7 male rhesus monkeys (Macaca mulatta) were given concurrent access to PCP and water under fixed ratio (FR) 8 schedules during 2 daily sessions that alternated with 2 sessions during which pellet deliveries were contingent on lever presses under an FR 64 schedule. After operant responding stabilized, PCP was replaced by water for 10 days, and food access remained under the same schedule. Subsequently, concurrent PCP and water access was reintroduced for 10 days. This procedure was repeated with 3 PCP concentrations (0.125, 0.25, and 0.50 mg/ml) and 3 FR requirements for food-reinforced responding (64, 128, and 256). Disruptions in operant responding for food served as a quantitative measure of withdrawal severity. During PCP withdrawal, males showed a greater suppression of food-maintained behavior than females at the 2 highest PCP concentrations and the lowest FR requirement tested. Males responded more than females for PCP; however, when weight was taken into consideration, PCP intake (milligrams per kilogram) in males and females was equal. The data suggest that males may experience more severe withdrawal effects than females, and the duration of the adverse effects of withdrawal lasts longer in males than in females. This study is the 1st to use nonhuman primates to document sex differences in withdrawal severity as measured by a quantifiable baseline. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Progressive neuropathologic lesions in vitamin E-deficient rhesus monkeys

A consistent group of progressive central and peripheral nervous system lesions developed in seven rhesus monkeys maintained on a vitamin E-deficient diet for 30 to 33 months. These lesions were absent from vitamin E-supplemented monkeys. The principal neuropathologic alteration was loss of sensory axons in the posterior columns, sensory roots, and peripheral nerves. Morphologic and morphometric studies indicated that the distal segments of the axons were affected most severely and large-caliber myelinated fibers are selectively involved. Swollen, dystrophic axons (spheroids) occurred infrequently. Degeneration and phagocytosis of small numbers of neuronal perikarya were observed in the dorsal root ganglia and the anterior horns. The number of affected neurons was not proportional to the number of affected axons. Accumulation of lipopigment was evident in neuronal perikarya and CNS endothelial cells. The nervous system lesion were usually accompanied by a chronic necrotizing myopathy. The neuropathologic lesions in vitamin E-deficient monkeys are compared with those in vitamin E-deficient rats and in humans with low serum vitamin E concentrations. A similar type of sensory axonopathy is associated with chronic deficiency of vitamin E in these three species.     

The development of stereoacuity in infant rhesus monkeys

The emergence of stereopsis at 3-4 months postnatal in human infants is striking and has led to speculation that its rapid onset and subsequent development must be due to a dramatic reorganization of the brain. Stereopsis has never been measured in infant monkeys, but previous studies have demonstrated that many other visual functions develop four times faster in infant monkeys than in humans. We made longitudinal assessments of stereoacuity in 11 infant rhesus monkeys. A forced-choice preferential-looking technique was used to present random-dot stereograms during testing. By 8 weeks after birth, all of the monkeys were responding to at least coarse levels of disparity (1760" [seconds]), and by 13 weeks of age, all were responding to the relatively fine level of 88" disparity. Age of onset for stereopsis in monkeys was at about one-quarter the age when it occurs in humans, as expected. However, subsequent development proceeded at a similar absolute rate in monkeys and humans. The findings are discussed relative to the neural mechanisms which might be responsible for the differing rates of development.     

Discriminative stimulus effects of delta 9-tetrahydrocannabinol and delta 9-11-tetrahydrocannabinol in rats and rhesus monkeys

Previous reports have suggested that delta 9-11-tetrahydrocannabinol (delta 9-11-THC), an exocyclic analog of delta 9-tetrahydrocannabinol (delta 9-THC), may have weak agonist effects as well as antagonistic properties. The purpose of the present study was to examine the effects of delta 9-11-THC in substitution and antagonism tests in rats and in rhesus monkeys trained to discriminate delta 9-THC from vehicle in two-lever drug-discrimination procedures. The substitution studies showed that delta 9-11-THC generalizes from the training dose of delta 9-THC in rats and in monkeys, although it was less potent in both species. The magnitude of the potency difference was greater in monkeys than in rats. When administered immediately following injection with the training dose of delta 9-THC, delta 9-11-THC failed to block the delta 9-THC cue in rats and showed a lack of dose-responsive inhibition in monkeys. These results suggest that delta 9-11-THC is devoid of antagonistic properties in the drug discrimination paradigm.     

Neuropathogenesis induced by rhesus cytomegalovirus in fetal rhesus monkeys (Macaca mulatta)

In a double-blind study, 655 sputum specimens were obtained from individuals suspected of having tuberculosis and were analyzed for the presence of Mycobacterium tuberculosis and rifampin susceptibility with use of a polymerase chain reaction (PCR)-based universal heteroduplex generator assay (PCR/UHG-Rif). Of the specimens containing viable M. tuberculosis, 100% of the smear-positive (n = 41) and 50% of the smear-negative (n = 6) specimens tested positive for the organism by PCR/UHG-Rif. Nineteen of 537 culture-negative specimens tested positive for M. tuberculosis by PCR/UHG-Rif and were from patients with confirmed tuberculosis who were receiving antituberculosis therapy at the time of specimen collection. Thirty-five specimens contained nontuberculous mycobacteria and were negative by PCR/UHG-Rif. Genotypic evidence of rifampin resistance in five of six culture-confirmed, rifampin-resistant isolates was obtained by PCR/UHG-Rif, yielding a sensitivity and specificity for the assay of 83% and 98.2%, respectively. These results demonstrate the feasibility of using a PCR-based assay directly on sputum specimens for simultaneous detection of M. tuberculosis and rifampin susceptibility, and they suggest that patients with smear-positive, untreated tuberculosis and those presenting with suspected drug-resistant tuberculosis are the most appropriate groups for testing by PCR/UHG-Rif.     

Effect of hunger on nonnutritive sucking in infant rhesus monkeys.

In Experiment I the thumbsucking of 5 Ss aged 90-180 days was measured at 0, 2.5, 7.5, and 10 hr. after feeding. In Experiment II these same Ss, now between ages 180 and 270 days, were observed at intervals of 0, 37.5, 75, 112.5, 250 min., and 10 hr. after feeding. In Experiment III 6 additional monkeys 90-180 days of age were observed at the 1st 5 intervals of Experiment II. In all experiments thumbsucking increased with hunger. In Experiment II there was no significant increase in sucking during the intervals between 0 and 250 min. Experiment III results showed a significant increase during this period suggesting that the effectiveness of specific deprivation intervals decreases with age. (16 ref.) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of differential pretraining on learning-set formation in rhesus monkeys.

Compared the rate of learning-set formation by 4 rhesus monkeys that had previously been pretrained on the win-stay component of the learning-set strategy (Group WS) to the rate evidenced by 4 others that had pretraining on the lose-shift component (Group LS). Differences between groups were small, and asymptotic levels were below those previously obtained by monkeys without pretraining. The negative transfer resulted from generalized tendencies to perseverate or shift (Groups WS and LS, respectively), regardless of response outcome. The former tendency dissipated relatively rapidly, while the latter persisted very markedly throughout the 400-problem learning-set series. It is noted that learning-set formation requires a balance between the win-stay and lose-shift components; however, the optimal ratio is unknown. (19 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Acute effects of caffeine on several operant behaviors in rhesus monkeys

The acute effects of 1,3-trimethylxanthine (caffeine) were assessed using an operant test battery (OTB) of complex food-reinforced tasks that are thought to depend upon relatively specific brain functions, such as motivation to work for food (progressive ratio, PR), learning (incremental repeated acquisition, IRA), color and position discrimination (conditioned position responding, CPR), time estimation (temporal response differentiation, TRD), and short-term memory and attention (delayed matching-to-sample, DMTS). Endpoints included response rates (RR), accuracies (ACC), and percent task completed (PTC). Caffeine sulfate (0.175-20.0 mg/kg, IV), given 15 min pretesting, produced significant dose-dependent decreases in TRD percent task completed and accuracy at doses > or = 5.6 mg/kg. Caffeine produced no systematic effects on either DMTS or PR responding, but low doses tended to enhance performance in both IRA and CPR tasks. Thus, in monkeys, performance of an operant task designed to model time estimation is more sensitive to the disruptive effects of caffeine than is performance of the other tasks in the OTB.     

Effects of clonidine, dexmedetomidine and xylazine on thermal antinociception in rhesus monkeys

The antinociceptive effects of the s.c. administration of the alpha-2 agonists clonidine (0.0032-1.0 mg/kg), dexmedetomidine (0.001-0.032 mg/kg) and xylazine (0.1-3.2 mg/kg) were examined in the warm-water tail withdrawal assay in rhesus monkeys. The three agonists were dose-dependently effective in this assay; their potency order being dexmedetomidine > clonidine > xylazine. The alpha-2 antagonist idazoxan (0.1-3.2 mg/kg) caused dose-dependent and roughly parallel rightward shifts in the dose-effect curves for the three agonists. Apparent pA2 analysis with idazoxan yielded homogeneous values for the three agonists, supporting the notion that similar receptors mediate their antinociceptive effects. The opioid antagonist quadazocine (1.0 mg/kg) did not antagonize the antinociceptive effects of clonidine and xylazine, indicating that opioid receptors do not participate in the effects of the compounds in this assay. At dose ranges found to be effective in the antinociceptive assay, clonidine, dexmedetomidine and xylazine also dose-dependently caused sedation, muscle relaxation, bradycardia and moderate respiratory depression. The sedative, muscle relaxant and respiratory depressant effects of xylazine could be antagonized by idazoxan, suggesting that these effects may be mediated through alpha-2 receptors. These data indicate that the three imidazoline alpha-2 agonists, clonidine, dexmedetomidine and xylazine are effective s.c. in the warm-water tail withdrawal assay in rhesus monkeys, but only at doses that produce other behavioral and physiological effects.     

Observational conditioning of snake fear in rhesus monkeys.

Hypothesized that observational conditioning is involved in the origins of many human and nonhuman primates' fears and phobias. In Exp I, a new index of snake fear in 7 19–28 yr old wild-reared rhesus monkeys and 9 laboratory-reared offspring (aged 8 mo to 6 yrs) was tested. Results show the measure was useful and demonstrated that young Ss raised by parents who had a fear of snakes did not acquire the fear in the absence of any specific experience with snakes. In Exp II, using 5 of the wild-reared Ss and 6 of the laboratory-reared Ss from Exp I, 5 of 6 offspring acquired an intense and persistent fear of snakes as a result of observing their wild-reared parents behave fearfully in the presence of real, toy, or model snakes for a short period of time. The fear was not context specific and showed no significant signs of diminution at 3-mo follow-up. (49 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Aging in rhesus monkeys: Different windows on behavioral continuity and change.

Rhesus monkeys were observed longitudinally from 6 to 20 years of age, the period encompassing early to late adulthood in this species. Repeated-measures analyses of the monkeys' behavioral repertoire revealed 3 quite different pictures of the aging process. First, there were significant systematic changes in the levels of many categories of behavior with increasing age, although the direction and timing of change varied from category to category. Second, for most categories, individual differences among the monkeys were highly stable from early to late adulthood. Finally, there was remarkable consistency within individual behavioral profiles across the entire study such that each monkey retained its distinctive behavioral features (personality) throughout its adult years. Thus, aging in rhesus monkeys is characterized by both continuity and change. (PsycINFO Database Record (c) 2010 APA, all rights reserved)