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Biomedical subjects

M E Carroll

Publications and source records attributed to M E Carroll.

At least 91 records · Page 5Linked to original sources
PubMed1985

Concurrent phencyclidine and saccharin access: presentation of an alternative reinforcer reduces drug intake.

Six monkeys self-administered orally delivered phencyclidine ("angel dust") and saccharin under concurrent fixed-ratio 16 schedules during daily three-hour sessions. Liquid deliveries were contingent upon lip-contact responses on solenoid-operated drinking spouts. Three saccharin concentrations (0.003%, 0.03% and 0.3%, wt/vol) were tested in a nonsystematic order. For each saccharin concentration, the following series of phencyclidine concentrations (mg/ml) was presented: 0.25, 0.5, 1, 0.25 (retest), 0.125, 0.0625, 0.0312, 0.25 (retest) and 0 (water with stimuli signaling phencyclidine). As the saccharin concentration increased, the number of drug deliveries decreased, and the peaks of the concentration-response functions were shifted to the right. The lowest saccharin concentration (0.003%, wt/vol) maintained responding in excess of phencyclidine levels in only one monkey. The two higher saccharin concentrations maintained behavior far in excess of phencyclidine, but saccharin deliveries decreased in some monkeys as phencyclidine concentration and intake (mg/kg) increased. The time course and patterns of phencyclidine-reinforced responding were also altered when saccharin was concurrently available. The results are discussed in terms of strategies to reduce drug-reinforced behavior, preference between different reinforcers, and measures of reinforcing efficacy.

Animals↗
PubMed1985

Performance maintained by orally delivered phencyclidine under second-order, tandem and fixed-interval schedules in food-satiated and food-deprived rhesus monkeys.

Three monkeys were each tested under a second-order fixed interval (FI) schedule with fixed-ratio (FR) components, a tandem FI FR schedule and an FI schedule while either food deprived or food satiated. Under the second-order schedule, every sixteenth lip-contact response on a drinking spout produced a brief stimulus and the first FR 16 begun and completed after the 60-min interval elapsed resulted in both the brief stimulus and access to orally delivered phencyclidine. The tandem schedule was similar, except that brief-stimulus presentations during the 60-min interval were omitted, and the third schedule was an FI 60 min. The reinforcer, orally delivered phencyclidine, was available only at the end of the 60-min session. The number of drug deliveries was either "limited" (300) or "unlimited" (for 1 hr) to determine whether increased responding due to food deprivation would occur in the absence of increased drug intake. Under all conditions response rates were nearly twice as high during food deprivation as they were during food satiation. The number of phencyclidine deliveries available at the end of the session has no systemic effect on the rate of pattern of responding, but quarter-life values were consistently lower during food deprivation than they were during food satiation. Under the tandem and FI schedules, overall response rates were much lower than under the second-order schedule, and quarter-life values were higher. When water was substituted for phencyclidine under each schedule condition, response rates and liquid deliveries generally declined to below phencyclidine levels indicating that the drug had been functioning as a reinforcer.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1984

Increased phencyclidine self-administration due to food deprivation: interaction with concentration and training conditions.

Six monkeys were trained to self-administer orally delivered phencyclidine (0.25 mg/ml) under a fixed-ratio 16 (FR-16) schedule. Water was concurrently available under an FF-16 schedule. During initial phencyclidine training, three monkeys were allowed free access to food (food satiation) and three were maintained at 85% of their free-feeding body weights (food deprivation). At the end of the training phase, the food-satiated monkeys were food-deprived. After behavior was stable for ten sessions, all monkeys were food-satiated and tested with a range of phencyclidine concentrations (0.0625-1 mg/ml). They were subsequently food-deprived and tested with concentrations of 0.0312-1 mg/ml, and then they were again food-satiated and tested with 0.0312 and 0.25 mg/ml. The monkeys that were trained to self-administer phencyclidine while food-satiated showed substantial phencyclidine-maintained responding at lower drug concentrations when later tested while food-satiated. In contrast, monkeys that were trained while food-deprived did not respond for phencyclidine in excess of water at the lower concentrations when later tested while food-satiated. Drug-maintained performance during food deprivation did not change systematically as a function of training condition (food deprivation versus food satiation). These results illustrated a marked interaction between drug concentration and the feeding condition and this interaction was modified by training history.

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↗
PubMed1984

Self-administration of orally-delivered methohexital in rhesus monkeys with phencyclidine or pentobarbital histories: effects of food deprivation and satiation.

Orally-delivered methohexital was demonstrated to function as a reinforcer for rhesus monkeys with either phencyclidine or pentobarbital self-administration histories. The effects of food deprivation and food satiation were compared across a wide range of methohexital concentrations. Initially, three monkeys were trained to orally self-administer phencyclidine (0.25 mg/ml) and water, and three were trained to orally self-administer pentobarbital (0.5 mg/ml) and water under concurrent fixed-ratio (FR) schedules during daily 3-hr sessions. Liquid deliveries during the session (drug and water) and intersession (water) were contingent upon lip contact responses on solenoid-operated drinking spouts. The monkeys were first tested while food deprived by maintaining them at 85% of their free-feeding body weights. Methohexital concentrations were presented in the following order, and each concentration was held constant until at least five or six sessions of stable behavior were obtained: 2, 2.8, 4, 2 (retest), 1, 0.5, (plus 0.25 and 0.125 in monkey M-W) and 2 (retest) mg/ml. The monkeys were then food satiated by allowing them unlimited access to food, and the methohexital concentration series was repeated. During food deprivation, the concentration-response functions generally resembled an inverted U. Concurrent water-maintained responding was generally low, but it increased in some monkeys as methohexital concentrations increased in some monkeys. During food satiation, methohexital-maintained responding was not different from water-maintained responding in some monkeys, but in others it was substantially higher than water-maintained responding. Maximum drug intake ranged from 20.4 to 93.8 mg/kg during food deprivation and from 6.4 to 64.2 during food satiation among the six monkeys.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1984

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)

Administration, Oral↗
PubMed1983

Oral d-amphetamine and ketamine self-administration by rhesus monkeys: effects of food deprivation.

Orally delivered d-amphetamine and ketamine were tested for their ability to maintain self-administration behavior by substituting them for phencyclidine. Six monkeys were trained to self-administer phencyclidine (0.25 mg/ml) and water under a concurrent fixed-ratio 16 schedule during 3-hr sessions. At the start of the experiment the monkeys were maintained at 85% of their free-feeding body weights. Liquid deliveries were contingent upon lip-contact responses on solenoid-operated drinking spouts. When d-amphetamine (0.0156-0.25 mg/ml) was substituted for phencyclidine, maximum drug intake ranged from 1 to 1.5 mg/kg among three monkeys, and response rates were greatest at the three lower concentrations (0.0156-0.0625 mg/ml). When monkeys were food satiated, maximum d-amphetamine intake ranged from 0.3 to 1.1 mg/kg among three monkeys, and response rates were greatest at the higher concentrations (0.125-0.25 mg/ml). In the second experiment, ketamine (0.125-4 mg/ml) was substituted for phencyclidine (0.25 mg/ml). Maximum ketamine intake ranged from 14.5 to 44.5 mg/kg among three monkeys, and maximum responding occurred at the 0.25- and 1-mg/ml concentrations. Food satiation reduced maximum ketamine intake (7.1-22.3 mg/kg) among three monkeys. With both d-amphetamine and ketamine, responding was evenly distributed throughout the session during food satiation, whereas during food deprivation, most responding occurred within the 1st hr of the session. These results showed that substitution procedures can be effectively used to demonstrate the reinforcing effects of orally delivered d-amphetamine and ketamine. Food deprivation generally increased drug-reinforced responding; however, at the higher concentrations of drug this difference was greatly diminished.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1982

Oral self-administration of phencyclidine analogs by rhesus monkeys: conditioned taste and visual reinforcers.

Three monkeys self-administered orally-delivered phencyclidine, 1-(1-phencyclohexyl) piperidine (PCP), N-ethyl-1-phencyclohexylamine (PCE), and 1-[1-(2-thienyl)cyclohexyl]piperidine (TCP) over a wide range of concentrations (0.0156, 0.0312, 0.0625, 0.125, 0.25, and 0.5 mg/ml). Water was also available under a concurrent fixed-ratio (FR) 16 schedule. Drug deliveries were substantially higher than concurrent water deliveries at all concentrations, indicating that the three compounds functioned as effective reinforcers. Maximum liquid deliveries occurred at concentrations of 0.0625 (PCP and TCP) and 0.125 mg/ml (PCE). TCP was much shorter-acting (10-15 min) than PCP (4-6h) based on observations of severe ataxia at high concentrations. To investigate the conditioned reinforcing effects of taste, a quinine solution (0.088 mg/ml) was substituted for PCP (0.25 mg/ml) in five monkeys. Four monkeys responded for quinine in excess of water for a range of seven to over 30 sessions, while one monkey (M-R) did not show any substantial responding for quinine. With the same five monkeys (treatment order mixed), the effect of visual stimuli was tested by substituting water for PCP while retaining the visual stimuli indicating drug availability. Four monkeys showed increased responding on the side signaling drug for only 0-4 sessions, while one monkey (M-R) showed persistent responding for water on the side with drug stimuli for 29 sessions. These results indicated that taste functioned as an effective conditioned reinforcer, while visual stimuli appeared to be less effective in the oral drug self-administration paradigm.

Administration, Oral↗
PubMed1982

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.

Animals↗
PubMed1982

Tolerance to the behavioral effects of orally self-administered phencyclidine.

Three rhesus monkeys self-administered fixed doses (4, 8 or 16 mg/kg) of an orally-delivered phencyclidine solution (0.25 mg/ml) under a one response, fixed-ratio (FR 1) schedule. They self-administered a saccharin 0.05% (wt/vol) solution, under an FR 8 schedule, 40 minutes after phencyclidine access began. After behavior stabilized over at least five daily sessions at each dose, water was substituted for phencyclidine for four sessions, and then phencyclidine was reinstated at the same dose, and behavior was allowed to stabilize. A comparison of saccharin-maintained behavior before and after the four sessions of water substitution yielded a two-fold shift in the dose effect curve indicating a rapid loss of tolerance to phencyclidine. Phencyclidine produced a biphasic effect on saccharin-maintained behavior: response rates increased at the low dose and decreased at the high dose. Subsequently, the FR requirement for saccharin was increased to 16 and the number of sessions of water substitution was varied: 1, 4, 8 or 16. The results indicated that tolerance was lost after four days of phencyclidine absence but not one, and complete tolerance was acquired within four to five days. This procedure produced a reliable measure of tolerance under limited access conditions whereby orally-delivered phencyclidine was also demonstrated to be functioning as a reinforcer.

Animals↗
PubMed1981

Determinants of increased drug self-administration due to food deprivation.

Changes in oral etonitazene self-administration were compared in four groups of rats that were maintained at 100, 95, 85, or 75% of their pre-experimental free-feeding body weights. Etonitazene (5 micrograms/ml) or water was available for 16 h according to a fixed-ratio (FR) 1 schedule. Each liquid delivery (0.1 ml) was contingent upon a lever-press response. During food deprivation etonitazene intake gradually increased to over two-fold as body weights decreased over 25 sessions; etonitazene intake was inversely proportional to body weight. The 75% weight group showed stereotypy, self-mutilation and large variability in daily etonitazene intake. In another experiment a range of deprivation conditions was studied in a group of six rats with etonitazene (5 micrograms/ml) or water available on an FR 8 schedule during 1-h sessions. When the rats were gradually food satiated, etonitazene-maintained behavior declined but remained higher than water-maintained behavior; however, when they were abruptly food satiated, etonitazene-maintained behavior decreased to low levels.

Animals↗
PubMed1981

A microcomputer system for the control of behavioral experiments.

A self-contained microcomputer control system (MCS) is described for controlling and recording events from behavioral experiments using a low-cost microcomputer, the Rockwell AIM 65, and the BASIC language. Features of the system include a printer, alphanumeric display, 4K RAM, 8K BASIC on read only memory (ROM), a cassette interface, a power supply, and a control interface, all contained in a compact enclosure. The control interface allows for 16 inputs and 16 outputs, and includes a real-time clock and versatile machine language subroutines for controlling and recording real-time events. These features make BASIC a suitable user language for this application. The use of this microcomputer control system for operant research in behavioral pharmacology is described.

Animals↗