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.     

Oral cocaine self-administration in rhesus monkeys: Strategies for engendering reinforcing effects.

Orally delivered cocaine was established as a reinforcer for 8 rhesus monkeys (Macaca mulatta). Initially, each monkey was given a choice between the water vehicle and a 0.2 mg/ml cocaine concentration. The 0.2 mg/ml solution was not consumed in preference to water. One or more acquisition procedures were used with each monkey to establish orally delivered cocaine as a reinforcer. A common feature of all but one procedure was environmental situations that lead to the elective drinking of the cocaine solution. Evidence confirming the establishment of cocaine's reinforcing effects was obtained by testing each monkey across a broad range of cocaine concentrations under conditions of concurrent access to the cocaine solution and vehicle. Over a range of concentrations, the monkeys obtained greater cocaine than vehicle deliveries. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Phentermine/fenfluramine decreases cocaine self-administration in rhesus monkeys

Dopaminergic agonists can decrease cocaine self-administration at doses that do not decrease food-maintained responding, a pre-clinical effect indicative of a potential treatment for human cocaine abuse. To assess whether similar effects could be obtained with medications currently used to treat substance abuse, phentermine and fenfluramine were given alone and in combination to rhesus monkeys responding under schedules of food and cocaine delivery. Phentermine decreased cocaine-maintained responding with no effect on food-maintained responding. Fenfluramine also selectively decreased cocaine-maintained responding, but only at the highest dose. Combining a lower dose of fenfluramine with phentermine selectively decreased cocaine-maintained responding, but not more than with phentermine alone. These results suggest that phentermine, as well as its combination with fenfluramine, may be useful in the treatment of cocaine abuse.     

Comparison of the effects of methamphetamine, bupropion, and methylphenidate on the self-administration of methamphetamine by rhesus monkeys.

The effectiveness of methadone as a treatment for opioid abuse and nicotine preparations as treatments for tobacco smoking has led to an interest in developing a similar strategy for treating psychostimulant abuse. The current study investigated the effects of three such potential therapies on intravenous methamphetamine self-administration (1 – 30 μg/kg/injection) in rhesus monkeys. When given as a presession intramuscular injection, a high dose of methamphetamine (1.0 mg/kg) decreased intravenous methamphetamine self-administration but did not affect responding for a food reinforcer during the same sessions. However, the dose of intramuscular methamphetamine required to reduce intravenous methamphetamine self-administration exceeded the cumulative amount taken during a typical self-administration session, and pretreatment with a low dose of methamphetamine (0.3 mg/kg) actually increased self-administration in some monkeys at the lower self-administration dose. Like pretreatment with methamphetamine, pretreatment with bupropion (3.2 mg/kg) decreased methamphetamine self-administration but did not affect responding for food. Pretreatment with methylphenidate (0.56 mg/kg) did not significantly alter methamphetamine self-administration. These results suggest that some agonist-like agents can decrease methamphetamine self-administration. Although the most robust effects occurred with a high dose of methamphetamine, safety and abuse liability considerations suggest that bupropion should also be considered for further evaluation as a methamphetamine addiction treatment. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Rhinal cortex lesions produce mild deficits in visual discrimination learning for an auditory secondary reinforcer in rhesus monkeys.

Aspiration, but not neurotoxic, lesions of the amygdala impair performance on a visual discrimination learning task in which an auditory secondary reinforcer signals which of 2 stimuli will be reinforced with food. Because aspiration lesions of the amygdala interrupt projections of the rhinal cortex traveling close to the amygdala, it was hypothesized that damage to the rhinal cortex would severely impair learning in this task. Rhesus monkeys (Macaca mulatta) were trained to solve visual discrimination problems based on an auditory secondary reinforcer, were given lesions of the rhinal cortex or the perirhinal cortex alone, and were then retested. The monkeys displayed a reliable, albeit mild, deficit in postoperative performance. It is concluded that the aspiration lesions of the amygdala that produced a severe impairment did so because they interrupted connections of temporal cortical fields beyond the rhinal cortex that are also involved in learning in this task. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Rhinal cortex ablations fail to disrupt reinforcer devaluation effects in rhesus monkeys (Macaca mulatta).

Studies have shown that excitotoxic lesions of the amygdala attenuate reinforcer devaluation effects in monkeys and rats. Because the rhinal (i.e., entorhinal and perirhinal) cortex has prominent reciprocal connections with the amygdala and has been suggested to store knowledge about objects, it is possible that it too composes part of the critical circuitry subserving learning about objects and their associated reinforcement value. To test this possibility, rhesus monkeys with rhinal cortex removals as well as unoperated controls were tested using a reinforcer devaluation procedure. Monkeys with rhinal cortex removals and controls, unlike those with amygdala lesions, tended to avoid displacing objects overlying a devalued food. These results indicate that the rhinal cortex is not a critical part of the neural circuitry mediating the effects of reinforcer devaluation. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The effects of a monetary alternative on marijuana self-administration

We have used a variety of methods to characterize the genome of the archaeon Methanosarcina thermophila TM-1. Pulsed-field gel analysis indicates a genome size of 2.8 Mb. We have constructed a bacterial artificial chromosome (BAC) library of M. thermophila and have used it to generate physical maps for this organism. The library is made up of 384 clones with an average insert size of 58 kb representing 8.0 genome equivalents. The utility of the library for low-resolution physical mapping was shown by identifying NotI linking clones and using these to order the NotI macrorestriction fragments of M. thermophila into a 2.8 Mb map. Hybridization of nine single copy genes and a 16S rRNA sequence to these macrorestriction fragments forms the basis for the first genetic map in this organism. High-resolution physical maps, consisting of overlapping clones, have been created using HindIII fingerprints of BAC clones. In this way, we identified a minimal path of five clones that span a 270 kb NotI fragment. The ease of manipulating BAC clones makes the BAC system an excellent choice for the construction of low-resolution and high-resolution physical and genetic maps of archaeal genomes. It also provides a substrate for future genome-sequencing efforts.     

Visual stimulation as a reinforcer in neonatally asphyxiated monkeys.

Compared the rates of response to visual reinforcers of 4 rhesus monkeys that had been asphyxiated at birth for 7-10 min. of secondary apnea to those of 4 controls. The neonatally asphyxiated Ss responded at higher rates than controls, and reduction in the complexity of the stimulus view led to decrements in this rate. In light of evidence demonstrating a sparing of the visual afferent system following asphyxiation at birth, it is suggested that the higher response rate of the asphyxiates is a function of motivational changes induced by neonatal asphyxia. (16 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.     

Drug-induced reinstatement of amphetamine self-administration behaviour in monkeys.

Stabilized and then extinguished the self-administration of d-amphetamine in 3 male squirrel monkeys. Ss were then pretreated with d-amphetamine, iv, before commencement of each daily session in an extended series. This led to consistent reinstatement of the characteristic pattern of drug self-administration behavior. The effect depended partially upon the amphetamine dose used as a pretreatment. Results from this and related experiments suggest that a complex relationship between external discriminative stimuli and amphetamine pretreatment forms the basis for drug-induced reinstatement of self-administration behavior. A "state-dependent" learning process may also be implicated. (French summary) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Behavioral evaluation of modafinil and the abuse-related effects of cocaine in rhesus monkeys.

Modafinil is a central nervous system stimulant used to promote wakefulness, and it is being evaluated clinically as an agonist medication for treating stimulant abuse. This is the first report of the effects of modafinil on the abuse-related effects of cocaine in nonhuman primates. The behavioral effects of modafinil were examined in three studies. First, the discriminative stimulus effects of modafinil (3.2–32 mg/kg) were evaluated in rhesus monkeys (Macaca mulatta) trained to discriminate either low (0.18 mg/kg, IM) or high (0.4 mg/kg, IM) doses of cocaine from saline. Modafinil dose-dependently substituted for cocaine in 6 of 7 monkeys. In the second study, the effects of chronically administered modafinil (32–56 mg/kg/day, IV) on food- and cocaine-maintained (0.001–0.1 mg/kg/inj) operant responding were examined. Modafinil was administered 3 times/hr for 23 hr/day to ensure stable drug levels. Chronic treatment with 32 mg/kg/day modafinil selectively reduced responding maintained by intermediate and peak reinforcing doses of cocaine, but responding maintained by higher doses of cocaine was unaffected. Food-maintained behavior did not change during chronic modafinil treatment. In a third study, modafinil (32 and 56 mg/kg/day, IV) was examined in a reinstatement model. Modafinil transiently increased responding during extinction. These findings indicate that modafinil shares discriminative stimulus effects with cocaine and selectively reduces responding maintained by reinforcing doses of cocaine. In addition, modafinil reinstated cocaine-seeking behavior, which may reflect its cocaine-like discriminative stimulus effects. These data support clinical findings and indicate that these preclinical models may be useful for predicting the effectiveness of agonist medications for drug abuse treatment. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Further analysis of S-R separation effects on visual discrimination performance on normal rhesus monkeys and monkeys with superior colliculus lesions.

Tested the orientation and attention hypotheses by requiring 4 monkeys with superior colliculus lesions and 2 controls to discriminate between stimuli presented in different parts of the visual field, at durations either too brief or sufficiently long to permit fixation. Findings indicate that before the lesions, Ss discriminated between 2 color-differentiated stimuli presented on a screen only when they fixated the center of the screen. The stimuli were presented 8, 20, or 32° from the screen's center, for 2 sec or 100 msec, a duration too brief to permit their fixation. Performance declined when the response sites, located either centrally or peripherally, were separated from the stimuli, whether they were presented for 2 sec or 100 msec. Findings suggest that the stimulus-response separation effect is due to selective attention to the response sites and not to fixating them during stimulus presentation. Following superior colliculus lesions, Ss were impaired in discriminating between peripheral stimuli, but only when they responded centrally. This deficit was not due to a failure to fixate the stimuli, for it occurred when the stimuli were 100 msec or 2 sec, or to reduced sensory capacities, since it disappeared when Ss responded peripherally. It is concluded that this deficit may reflect deficient attentional shifts from the response sites to the stimuli. (17 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Short- and long-term effects of repetitive mother–infant separations on social development in rhesus monkeys.

Rhesus monkey mother–infant dyads were each subjected to 16 4-day physical separations between the infants' 3rd and 9th mo of life. Infants displayed protest behavior following each separation but only minimal signs of despair. Their protest diminished somewhat over repeated separations. The mothers' separation reactions were considerably milder (and changed little) over repeated separations. The separations appeared to retard the development of normal mother–infant relationsips: Relative to nonseparated control dyads, separated infants displayed excessive levels of infantile behaviors, although their mothers did not differ from control mothers in levels of any behavior. Near the end of their 1st yr, all infants were permanently separated from their mothers and housed as peer groups. Over the next 30 wks during peer housing, few behavioral differences emerged between previously separated and control Ss. However, when exposed to their mothers during preference tests, previously separated Ss seemed to avoid their mothers in sharp contrast to the mother-seeking activity displayed by control infants. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Contrasting effects of lateral striate and superior colliculus lesions on visual discrimination performance in rhesus monkeys.

Tested 3 rhesus monkeys with lesions of lateral striate cortex (LSC), 4 monkeys with superior colliculus (SC) lesions, and 3 unoperated monkeys for retention of a preoperatively acquired pattern discrimination. The 3 groups of monkeys were then tested in 2-choice, color discrimination tests, 1 involving varying degrees of stimulus–response (S–R) separation and the other, administered several months later, involving various directions of S–R separation. Ss were also tested in a series of 2-choice pattern discriminations, following each of which they were tested for relearning when the patterns were masked with bars or circles. LSC lesioned Ss were moderately retarded in retention of the pattern discrimination, whereas those with SC lesions were not. SC lesioned Ss, but not those with LSC lesions, were impaired in both S–R separation tests, which demonstrates that their deficit was not transient or solely due to a difficulty in shifting the gaze in 1 direction. The LSC Ss, unlike those with SC lesions, were deficient in relearning discriminations between masked patterns. Findings suggest that SC and LSC may be involved in 2 different aspects of attention, respectively: shifting attention (and orientation) from 1 spatial locus to another and maintaining attention on fixated stimuli. (40 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Neonatal lensectomy and intraocular lens implantation: effects in rhesus monkeys

PURPOSE: To compare the effects of a lensectomy with and without intraocular lens (IOL) implantation on a neonatal rhesus monkey eye. METHODS: A lensectomy and anterior vitrectomy was performed on 75 monkeys during the first 16 days of life; 21 of these monkeys also had an IOL implanted into the posterior chamber. The eyes were examined at regular intervals using biomicroscopy, applanation tonometry, and ophthalmoscopy. RESULTS: The pseudophakic monkeys were studied until they were 92.5 +/- 5.8 weeks of age and the aphakic monkeys until they were 80.4 +/- 5.7 weeks of age. Pupillary membranes (100% versus 55.5%; P < 0.01) and lens regeneration into the pupillary aperture (28.6% versus 5.6%; P = 0.02) occurred more often in the pseudophakic than the aphakic eyes. As a result, the pseudophakic eyes required more reoperations than the aphakic eyes to keep the visual axis clear (P < 0.01). There was not a significant difference in the incidence of ocular hypertension between the pseudophakic and aphakic eyes (9.5% versus 12.7%; P = 0.34). Pupillary capture of the IOL optic occurred in 52% and haptic breakage in 33% of the pseudophakic eyes. All of the eyes with broken haptics had a prominent Soemmerring's ring varying in maximum thickness from 0.6 to 2 mm. Nine of the haptics from the seven eyes with broken IOLs had eroded into the iris, two into the ciliary body, and one into the anterior chamber. CONCLUSIONS: Implanting an IOL into a neonatal monkey eye after a lensectomy and anterior vitrectomy increases the likelihood of a reoperation being necessary. Haptics frequently erode into the iris and ciliary body and may break because of stress placed on the optic-haptic junction by forward movement of the IOL.     

Effects of kappa opioid agonists on the discriminative stimulus effects of cocaine in rhesus monkeys.

The study examined the effects of the kappa opioid agonists U50,488 and ethylketocyclazocine (EKC) on cocaine discrimination in rhesus monkeys trained to discriminate cocaine (0.4 mg/kg) from saline. Administration of U50,488 and EKC alone produced primarily saline-appropriate responding. Kappa agonist pretreatments produced variable effects on cocaine discrimination across monkeys, attenuating the discriminative stimulus effects of cocaine in some monkeys, but either having no effect on cocaine discrimination or enhancing the discriminative stimulus effects of cocaine in other monkeys. The effects of kappa agonists on cocaine discrimination were reversed by pretreatment with the opioid antagonist naloxone (1.0 mg/kg). These results indicate that kappa agonists do not consistently block the discriminative stimulus effects of cocaine in rhesus monkeys. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Transfer effects of cue-related movement reversal in discrimination reversal learning with rhesus monkeys.

Investigated the relative influence of directional movement reversal on the learning of discriminations and discrimination reversals using 36 macaque monkeys in 2 experiments. The learning tasks involved comparisons among movement feedback, brightness, and spatial location as discriminanda. Results indicate that differential directional movements, when related to or serving as discriminative cues, produce a persistent elevated level of postreversal errors within a discrimination reversal task. Further, the brightness dimension was relatively easy for reversal and generally superior to spatial location and movement feedback. It is suggested that the transfer difficulty produced by cue-related differential movement might be attributed to proactive interference from the reorganization of response-response sequences within the response. (16 ref.) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

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)     

Morphological and functional effects of intranigrally administered GDNF in normal rhesus monkeys

Effects of a single injection of either 150 micrograms human recombinant glial cell line-derived neurotrophic factor (rGDNF) or vehicle into the right substantia nigra were analyzed in 12 normal adult female rhesus monkeys. The studies included evaluating whole animal behavior, electrochemical recordings of striatal dopamine release, neurochemical determinations of basal ganglia and nigral monoamine levels, and immunohistochemical staining of the nigrostriatal dopamine system. The behavioral effects over the 3-week observation period following trophic factor administration were small, with blinded observers unable to distinguish between GDNF- and vehicle-treated animals. Quantitative measurements did show that five of six trophic factor recipients experienced some weight loss and four of the six GDNF recipients displayed small, but significant, increases in daytime activity levels. In vivo electrochemical recordings in the ipsilateral caudate and putamen 3 weeks after GDNF administration revealed increased potassium-evoked release of dopamine in trophic factor recipients. In a second series of animals killed at the same time, dopamine levels in the substantia nigra and ventral tegmental area of GDNF recipients were significantly increased, with ipsilateral values more than 200% higher than contralateral and control levels. Levels of the dopamine metabolite HVA were significantly elevated in the substantia nigra, ventral tegmental area, and caudate nucleus ipsilateral to the trophic factor injection. There was a trend toward increased HVA levels in the ipsilateral putamen, nucleus accumbens, and globus pallidus in GDNF-treated animals, but the ratios of HVA to dopamine were not significantly different between vehicle- and GDNF-treated recipients. Although some tissue damage from the delivery of concentrated trophic factor was evident, dopamine neurons remained in an adjacent to the injection site. In the substantia nigra ipsilateral to GDNF administration, dopamine-neuron perikaryal size was significantly increased, along with a significant increase in tyrosine hydroxylase-positive axons and dendrites. We conclude that, in the adult rhesus monkey, a single intranigral GDNF injection induces a significant upregulation of mesencephalic dopamine neurons which lasts for weeks.