Rapid acquisition of oral phencyclidine self-administration in food-deprived and food-satiated rhesus monkeys: Concurrent phencyclidine and water choice

Eight rhesus monkeys were trained to self-administer orally-delivered phencyclidine, with water concurrently available, under a fixed ratio (FR) schedule during daily 3-hr sessions. Liquid deliveries (0.55 ml) were contingent upon lip-contact responses on solenoid-operated drinking spouts. During the sessions, phencyclidine and water were available under FRs ranging from 1 to 16. Water was always available between sessions (FR 1), and food initially was available 24 hr/day. In Experiment 1 the monkeys initially were given access to water (FR 1) during the 3-hr sessions. Subsequently, phencyclidine (0.25 mg/ml) was substituted for water, and the monkeys were reduced to 85 percent of their free-feeding weights. The FR value was then increased from 1 to 8. Next, the monkeys received concurrent access to water from one spout and phencyclidine from the other (each under the FR 8 schedule), then the FR value was increased to 16 for both drug and water. Orally-delivered phencyclidine was rapidly demonstrated to function as a reinforcer (37.2 sessions) without using food to induce drinking. In Experiment 2 a similar procedure was used for another group of monkeys, except the monkeys remained food satiated throughout the acquisition phase. Phencyclidine was rapidly demonstrated to function as a reinforcer (25.9 sessions), although intakes were lower than in Experiment 1. After concurrent phencyclidine- and water-maintained performance stabilized at FR 16, the monkeys were food deprived, and phencyclidine intake increased to the levels reported in Experiment 1. Food deprivation greatly enhanced the reinforcing effect of phencyclidine and changed the temporal pattern of responding, but neither food deprivation nor food-induced drinking were necessary conditions to demonstrate the drug's reinforcing effects.     

Comparison of opioid agonists in maintaining responding and in suppressing morphine withdrawal in rhesus monkeys

Sixteen opioid agonists were studied for their capacity both to maintain responding previously reinforced by codeine and to suppress the withdrawal syndrome induced by morphine deprivation in rhesus monkeys. All compounds, which included examples from each of the major chemical families of opioids, maintained responding at rates above those maintained by saline. There were differences among the compounds in the maximal response rates maintained, and large differences in their potencies in maintaining responding. In morphine-dependent monkeys, the abstinence signs that developed 14 h after the last morphine dose were suppressed completely by all of the compounds except codeine. There was a strong positive correlation (r=0.92) between the potency of a compound in maintaining drug-reinforced responding and the potency of the compound in suppressing the morphine withdrawal syndrome.     

Lateralization for orientation in split-brain monkeys

Split-brain monkeys learned with each cerebral hemisphere to discriminate lines differing in slope by 15°. This type of spatial discrimination is usually performed better by the right hemisphere of humans. The left hemisphere of 8 monkeys learned this type of problem much more readily than did the right hemisphere. Learning to discriminate simple patterns in the same apparatus was done equally well by either hemisphere, demonstrating that the lateralized ability is specific to the stimuli employed.     

Discriminative stimulus properties of phencyclidine and five analogues in the squirrel monkey

Squirrel monkeys were trained to discriminate 0.16 mg/kg of 1-(1-phenylcyclohexyl) piperidine (PCP) from saline in a two-lever drug discrimination task on a fixed-ratio 32 schedule of food presentation. Intramuscular injections were given 5 min pre-session in a double alternation pattern. After reliable discriminative control of lever choice was established, dose-response determinations for generalization to the training dose of PCP were made with several doses of PCP, N-ethyl-1-phenylcyclohexylamine (PCE), 1-[1-(2-thienyl) cyclohexyl] piperidine (TCP), 1-(1-phenylcyclohexyl) morpholine (PCM), 1-(1-phenylcyclohexyl) pyrrolidine (PHP), and ketamine. All drugs produced dose-dependent PCP-appropriate responding. For each analogue, a dose was found which produced stimulus control of responding comparable to that of the PCP training dose. ED50 values were determined for each drug for percent drug-lever appropriate responding and for suppression of operant responding during test sessions. The relative potency for producing drug-lever appropriate responding was: TCP>PCP=PCE>PHP>PCM>ketamine. The relative potency for suppression of operant responding was: PCP=TCP>PHP>PCE>PCM>ketamine. In all cases, the dose necessary to suppress operant responding to fifty percent of vehicle rates was three to five times larger than the ED50 dose for drug-lever appropriate responding. The results of this study indicate marked similarities in the behavioral effects of these six arylcyclohexylamines.     

Cardiac Arrhythmias in Infant Pigtail Monkeys Following Maternal Separation

The occurrence of nocturnal cardiac arrhythmias was determined in 9 infant pigtail (M. nemestrina) monkeys during 3 baseline normal nights, 3 nights following maternal separation, and 3 nights following reunion with the mother. All infants lived in social groups where they had been raised by their natural mothers; heart rate data were collected by means of totally implantable biotelemetry systems. Marked individual differences were found in the mean frequency of cardiac arrhythmias in the baseline condition, and infants with lower heart rates had a greater mean number of arrhythmias. Maternal separation was accompanied by both increases in arrhythmias and decreases in heart rate. The relationship (slope of the regression line) between arrhythmias and heart rate changed in 8 of the 9 infants during separation, suggesting that the increase in arrhythmias was greater than could be accounted for by the decreases in heart rate alone. While both heart rate and arrhythmia values tended to return to baseline values following reunion with the mother, some infants exhibited prolonged separation-induced alterations.     

Behavioural and endocrine effects of naltrexone in male talapoin monkeys

The effect of treating captive male talapoin monkeys with naltrexone hydrochloride (500 μg/kg intra-muscular injection twice daily) was studied both in socially living and singly caged animals. The behaviour of the group males and endocrine changes in all treated animals were monitored during the course of treatment and on drug withdrawal. Naltrexone significantly reduced sexual behaviour in previously active males, while increasing grooming interactions. Aggressive behaviour did not change. There was an overall significant elevation in testosterone, LH and cortisol during drug treatment and a significant decrease on withdrawal. Changes in prolactin in response to naltrexone depended upon the pre-treatment level of this hormone; in males in which levels were low, there was a significant elevation in prolactin, while in those with high pre-treatment prolactin, levels were unchanged by the drug. The behavioural changes reported for this primate are in direct contrast to changes reported in rodents, while the hormonal changes, except for prolactin, are comparable to others reported.     

Establishing and maintaining clinically healthy gingivae in Rhesus monkeys

The aim of the present investigation was to determine a method and a minimal frequency of plaque removal for the establishment and maintenance of clinically healthy gingivae in Rhesus monkeys. Six adult, male monkeys were used and divided into three groups. In each group different methods were used for plaque removal. Frequencies of plaque removal of one, two and three times per week for consecutive weeks were tested. The results showed that gingival health could be established and maintained with any of the methods used (toothbrushing and interdental flossing: toothbrushing and a 3-min application of 2% chlorhexidine gluconate) but only when plaque was removed 3 times a week. This frequency of plaque removal sessions is discussed in relation to the necessity for sedation of the animals with possible adverse side effects.     

Periapical reactions to calcium hydroxide-containing sealers and AH 26® in monkeys

Abstract The long-term effect on periapical healing (8-14 months) of CRCS® and Sealapex® was compared with that of AH 26®. Vital pulpectomy and root canal filling by the hybrid ther-momechanical method were performed in teeth of 3 young monkeys. Ten roots with CRCS, 10 with Sealapex and 7 roots with AH 26 were examined after demineralization and routine histological processing. Hematoxylin and eosin and Brown & Brenn staining for micro-organisms were employed. Mild to severe inflammatory lesions were found at the apical foramina of the roots filled with AH 26 and CRCS. Most of the Sealapex specimens showed no inflammatory cells, except macrophages with sealer particles. A striking finding was a tendency towards apical obliteration with calcified tissue in roots filled with Seal-apex, apparently following resorption of the sealer. Such a tendency was seldom observed with the other sealers. However, both AH 26 and Sealapex were irritating for a long time when pushed into bone. Despite the interesting results with Sealapex, additional research is needed before its use can be unconditionally recommended. This sealer has not yet been tested in infected cases and its ability to be resorbed, which is an advantage when it precedes replacement by calcified tissue, may become a disadvantage if it is not followed by apical obliteration.     

Autoimmune encephalomyelitis in rhesus monkeys induced by immunization with cerebral endothelial cell membrane

Summary It is postulated that multiple sclerosis might be an autoimmune demyelinating disease of the central nervous system (CNS). The mechanisms involved are unknown but, since the blood-brain barrier (BBB) is damaged, injury to endothelial cells is likely to have occurred. Our previous studies have led us to investigate the autoimmune effect of injuring the blood-brain barrier by immunizing rhesus monkeys with an endothelial cell membrane from the same kind of animals. The immunized animals developed a chronic or a relapsing neurological illness. Histological and ultrastructural examinations of the brain in the acute stage showed infiltrates of mononuclear cells around the blood vessels of the white matter of cerebrum, cerebellum, pons and midbrain, while in the chronic phase, large areas of demyelination and remyelination, especially in the white matter regions, were present. The animals immunized with extraneural antigen, an endothelial cell membrane obtained from human umbilical cord, developed no neurological illness. This results indicate that the brain endothelial cell membrane has an inflammatory encephalitogenic activity which could produce widespread demyelination in animals. The animal model described here may prove to be useful in the pathogenetic investigation of human autoimmune demyelinating diseases.Supported by the Intractable Disease Division, Public Health Bureau, Japanese Ministry of Health and Welfare, the grants (61570385, 63570363) from Japanese Ministry of Education     

The effect of second-order schedule history on fixed-ratio performance maintained by orally-delivered phencyclidine in rhesus monkeys

Thirteen monkeys were trained to self-administer orally-delivered phencyclidine (0.25 mg/ml) and water under a concurrent fixed ratio (FR) 16 schedule. Phencyclidine was available from one lip-operated drinking device and water was available from another drinking device during daily 3-hr sessions. Seven monkeys were trained to respond under a second-order FR 240 (FR 20: brief stimulus) schedule. Upon completion of 4800 responses, the monkeys were allowed to self-administer 300 phencyclidine deliveries under an FR 1 schedule. After a mean of 33.3 sessions of second order schedule training, including 10 sessions at the terminal parameter, the monkeys were returned to the concurrent FR 16 schedule. Phencyclidine-maintained responding persisted at rates that were 42 percent higher than before second-order schedule training; however, concurrent water-maintained behavior increased only slightly. A second group of three monkeys were treated in an identical manner except that during second-order schedule training they received a saccharin solution (0.05%, wt/vol) instead of phencyclidine. After a mean of 30 sessions of second-order schedule training, including 10 sessions at the terminal parameter, the monkeys were returned to the concurrent FR 16 schedule, and there was no consistent change in phencyclidine or water deliveries. A third group of three monkeys received 300 phencyclidine deliveries at the same time after session onset and for the same total number of sessions as the monkeys that received second-order schedule training with phencyclidine; however, this group was not required to respond under the second-order schedule to gain access to the phencyclidine deliveries.(ABSTRACT TRUNCATED AT 250 WORDS)