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Biomedical subjects

M E Carroll

Publications and source records attributed to M E Carroll.

At least 73 records · Page 4Linked to original sources
PubMed1990

Effects of carbamazepine on self-administration of intravenously delivered cocaine in rats.

Carbamazepine (Tegretol) is widely used therapeutically as an anticonvulsant. Based on an hypothesis that links electrical kindling in the limbic system (leading to seizures) to reverse tolerance or sensitivity to cocaine's effects, carbamazepine is being tested as a treatment for human cocaine users. The purpose of this experiment was to examine the effects of carbamazepine on intravenous cocaine self-administration in rats. Rats self-administered intravenously delivered cocaine (0.2 mg/kg) under a fixed-ratio 4 schedule. When cocaine injections reached stable levels, carbamazepine was mixed with the rats' food for 8 days. Three doses of carbamazepine were tested (80, 120, and 160 mg/kg) in different groups of 5 rats each. The rats were later separated into groups with a high (greater than 750 infusions) and a low (500-750 infusions) cocaine baseline. Two control groups of 5 rats each received carbamazepine treatments (120 or 160 mg/kg) and self-administered an orally delivered solution of glucose and saccharin (G + S). At the highest carbamazepine dose in the high cocaine baseline group, carbamazepine reduced cocaine infusions by at least 50 percent and food intake by approximately 25 percent during the 8 days of treatment. Cocaine infusions returned to baseline within 24 hr after the regular diet was restored. Carbamazepine had a minimal effect in groups of rats with lower cocaine baselines. Responding reinforced by the G + S solution was reduced by both the 120 and 160 mg/kg carbamazepine doses. Water intake was not systematically affected by the addition of carbamazepine to the food; however, activity measures were significantly lower in some groups at the higher carbamazepine doses.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Fluoxetine reduces intravenous cocaine self-administration in rats.

Rats self-administered intravenously delivered cocaine (0.2 mg/kg) under a fixed-ratio (FR) 4 schedule during 24-hr sessions. Water was freely available from both a drinkometer and a standard water bottle. After behavior had stabilized, the rats were injected with fluoxetine HCl at 10:00 a.m. and 4:00 p.m. for 5 consecutive days. Three groups of 5 rats each received a different dose of fluoxetine (2.5, 5 or 10 mg/kg) via the IV cannula. In three other groups of rats a glucose and saccharin solution (G + S) was substituted for water in the automatic drinking device and saline was substituted for cocaine. These three groups of rats received the same fluoxetine doses as the cocaine self-injecting groups. In two additional groups of 5 rats each, the cocaine dose was changed to 0.1 or 0.4 mg/kg, and 5 mg/kg fluoxetine injections were given. The two higher doses of fluoxetine (5 and 10 mg/kg) reduced cocaine infusions (0.2 mg/kg) by at least 50 percent on all 5 days of treatment, and cocaine infusions returned to baseline levels within 48 hr after fluoxetine treatments were terminated. Behavior maintained by the G + S solution was also reduced by the two higher fluoxetine doses; however, this reduction did not reliably occur until the last two days of fluoxetine administration. The G + S intakes returned to baseline levels within 24 hr after fluoxetine treatment. Fluoxetine also reduced cocaine infusions in the group of rats that received the lower unit dose of cocaine (0.1 mg/kg); however, it had almost no effect on behavior maintained by a higher cocaine dose (0.4 mg/kg).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

PCP and hallucinogens.

In this review phencyclidine and related arylcyclohexylamines and hallucinogens, using LSD as the prototype, are considered as two distinct classes of abused drugs. Within these classes drugs that are found on the street are discussed, and a current epidemiological summary is provided. The abuse liability and dependence potential of these drugs are evaluated by considering four major determinants of their abuse. First, is the ability of a drug to function as a positive reinforcer and increase the probability of operant behavior leading to its delivery. Animal data describing the reinforcing effects of PCP are reviewed with respect to the influence of variables controlling drug-reinforced behavior; however, there are no animal models of hallucinogen-reinforced behavior. Several methods of quantifying reinforcing efficacy are discussed. A second determinant is the subjective effects of the respective drugs. These effects are described and compared across drugs based on clinical reports in humans and drug discrimination studies in animals. A third determinant is the behavioral and physiological toxicity that results from acute and chronic use of these drugs. Clinical reports and results of sensitive tests that have been developed for laboratory animals are reviewed. A fourth determinant is the dependence potential that exists with these drugs, measured by tolerance development and the extent to which behavioral and physiological disturbances occur when drug use is terminated.

Affect↗
PubMed1990

The behavioral pharmacology of alcohol and other drugs. Emerging issues.

Alcohol and other drugs are compared with respect to their abuse liability and dependence potential. Drug-reinforced behavior is defined, and factors related to the establishment of this behavior that have received increasing experimental attention in recent years are reviewed. Acquisition techniques, schedule of access, route of self-administration, and organism factors, such as species, gender, and genetic background, are discussed. Other areas of emerging interest are the effect of feeding regimens, alternative reinforcers, and social conditions on drug-reinforced behavior. Also, biochemical factors such as neurochemical alterations, hormonal changes, and alcohol and other drug combinations, are considered. Finally, dependence potential is considered in terms of observational changes and performance alterations that seem to be sensitive indicators of the protracted aspects of drug withdrawal. The relationship between drug-seeking behavior and withdrawal is examined.

Alcohol Drinking↗
PubMed1989

A concurrently available nondrug reinforcer prevents the acquisition or decreases the maintenance of cocaine-reinforced behavior.

Lever-pressing responses of 55 rats were reinforced with IV-delivered cocaine (0.2 mg/kg) or saline under conditions of continuous access for 15 24-h sessions. The rats also responded on tongue-operated drinking devices for deliveries of a 3% (w/v) glucose + 0.125% (w/v) saccharin (G+S) solution or water. The effects of removing these substances on behavior maintained by G+S, water, cocaine, or saline were compared in 11 groups. Terminating cocaine access produced a decrease in G+S drinking and an increase in food and water intake. In contrast, a group of rats that did not initially self-administer G+S showed increases in G+S drinking when cocaine was removed, and G+S-maintained responding persisted when cocaine was reinstated. Substitution of water for G+S produced a nearly two-fold increase in cocaine-reinforced behavior but no change in IV-delivered saline self-administration in a control group. A group that did not initially self-administer cocaine increased its infusion rate to over 400 infusions per day as soon as G+S was replaced with water. The effect of presenting cocaine to a group that responded for G+S alone was to decrease G+S intake, but there was only a transient decrease in water intake in the control group. Likewise, presentation of G+S to a group of rats self-administering cocaine resulted in a decrease in infusions, but saline infusions did not change in a control group. Generally, there was an increase in food and water intake during cocaine removal, but food and water intake did not vary systematically with the removal or presentation of G+S.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Nicotine dependence in rats.

Health hazards associated with nicotine and tobacco use are well known. A contributing factor, the dependence producing potential of this drug, has become widely accepted. However, there are only a few human and animal studies that provide objective measures of the behavioral consequences of nicotine abstinence. The purpose of the present experiment was to use sensitive measures to examine behavioral disruptions that resulted when nicotine administration was terminated. Six rats were administered 96 daily intravenous infusions of nicotine (0.125 mg/kg/infusion) for at least 10 days. They were trained to respond on a tongue-operated solenoid-driven drinking device that delivered 0.005 ml of a glucose and saccharin solution (G + S) per lick. When nicotine access was terminated for six days, there was a marked suppression in behavior reinforced by the sweetened solution, and this disruption was immediately reversed when nicotine was reinstated. In contrast, nicotine removal also resulted in a decrease in food intake on the first day, but on subsequent days food intake was significantly higher than when nicotine was administered. When cotinine (0.25 mg/kg/infusion), a metabolite of nicotine was substituted for nicotine for six days, similar disruptions resulted in responding maintained by G + S, but food intake was not significantly decreased on the first day of nicotine abstinence. These findings illustrate the utility of sensitive behavioral tests to reveal effects of nicotine abstinence.

Animals↗
PubMed1989

Effects of environmental conditions on the psychological well-being of primates: a review of the literature.

Amendments made to the Animal Welfare Act in 1985 require primate researchers to provide "a physical environment adequate to promote the psychological well-being of primates". Regulations have not yet been promulgated, in part because "the psychological well-being" of primates is extremely difficult to define. Ideally, those regulations would be based upon observable changes in behavior rather than assumed psychological changes. Regardless, new primate care regulations pertaining to social environment, cage size, exercise and other forms of environmental enrichment are anticipated. A review of the literature suggests that there is little scientific data to support changing existing regulations. For instance, although it is clear that total social isolation in very young primates can be behaviorally devastating in terms of normal social behaviors, there are few, if any, demonstrable adverse effects of individual housing in adult primates. On the other hand, group housing, particularly with groups changing frequently in composition, increases aggression, trauma and disease transmission. In addition, existing research suggests there are important species differences in terms of social preferences. It is impossible to justify an increase in cage size based upon the available literature. An additional practical consideration is that any change in cage size requirements will necessitate replacement of current primate housing on a national level, an enormously expensive proposition. Regarding environmental enrichment, research suggests that providing a naturalistic environment is not as critical as arranging dynamic events that are contingent upon behavior. However, new research is necessary to specify the types of environmental enrichment that are valuable and appropriate before useless, even damaging, and expensive changes are mandated.

Animal Welfare↗
PubMed1988

Behavioral dependence on caffeine and phencyclidine in rhesus monkeys: interactive effects.

Five rhesus monkeys were trained to self-administer orally-delivered phencyclidine (PCP) and water under concurrent fixed-ratio (FR) 8 schedules. Liquid deliveries were contingent upon lip-contact responses on solenoid-operated drinking spouts, and food pellet delivery was contingent upon responses on a centrally-located lever. Food was available during three 1-hr periods each day under an FR 64 or FR 80 schedule. The liquids were available during three 6.5-hr periods after each food component. In the first experiment caffeine (4 or 8 mg) was added to each 6-g food pellet, and after responding stabilized, noncaffeinated pellets were substituted for the caffeinated pellets for eight days. There were no differences in food-, water- or PCP-maintained behavior due to caffeine concentration (4 vs. 8 mg/pellet) although the monkeys consumed twice as much caffeine at the higher concentration. Food-maintained responding was reliably reduced by 25-50 percent the first day of caffeine removal, and there was a recovery of responding characterized by intermittent cycles of low response rates over the next 7 days. Water and PCP intake were not systematically disrupted when caffeine access was terminated. In the second experiment the monkeys were tested with caffeinated (6 mg/pellet) and noncaffeinated pellets under conditions of PCP removal (water substitution) and reinstatement. Under both food conditions, when PCP access was terminated, pellet deliveries decreased by about 50 percent and gradually recovered over the 8-day water substitution phase. However, behavioral disruptions were more severe under conditions in which monkeys received caffeinated pellets, suggesting an interactive effect due to termination of PCP access and decreased caffeine intake. These results indicate that disruptions in operant baselines are sensitive indicators of the effects of discontinuing caffeine access; however, the severity and time course of behavioral disruptions due to caffeine removal are considerably less than after termination of PCP access.

Animals↗
PubMed1988

Oral self-administration of N-allylnormetazocine (SKF-10,047) stereoisomers in rhesus monkeys: substitution during phencyclidine self-administration and withdrawal.

Orally-delivered N-allylnormetazocine (NANM) and its isomers were tested for their ability to function as reinforcers by substituting them for phencyclidine (PCP). Two monkeys were trained to self-administer PCP (0.25 mg/ml) and water under concurrent fixed-ratio (FR) 16 schedules during 3-hr sessions. Liquid deliveries were contingent upon lip-contact responses on solenoid-operated drinking devices. When the dextro (+)-isomer of NANM (0.062-1 mg/ml) was substituted for PCP, response rates increased and then decreased in an inverted U-shaped concentration-response function with peak response rates comparable to those maintained by PCP. Drug intake ranged from 2.8 to 25.7 mg/kg across the two monkeys and five concentrations. Water-maintained responding was considerably lower than drug-maintained behavior indicating that NANM was functioning as a reinforcer. As previously reported for PCP, almost all of the (+)-NANM was self-administered during the first half of the session. Substitution of the levo (-)-isomer of NANM resulted in an immediate decline to low response rates that were not distinguishable from those maintained by water. The racemic form (+/-) of NANM was also not self-administered in excess of concurrent water. In the second experiment concurrent PCP- and water-maintained responding were reestablished under FR 8 schedules during three 6.5-hr sessions daily. Food (6 g/pellet) was available under FR 64 and FR 80 schedules during three 1-hr sessions immediately preceding the liquid components. Water was then substituted for PCP for four days and PCP, (+)-, (-)- or (+/-)-NANM were reinstated in subsequent replications of the experiment.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1987

Cocaine withdrawal produces behavioral disruptions in rats.

There is currently no laboratory or clinical evidence from animal or human studies documenting a withdrawal syndrome associated with cocaine dependence, although many users report that withdrawal disturbances are responsible for their repeated use of the drug. In the present study rats self-administered i.v. cocaine and a sweetened drinking solution. When cocaine access was terminated there was a marked suppression in operant behavior reinforced by the sweetened solution, and this withdrawal disruption was immediately reversed when cocaine was reinstated. There were no physical signs of withdrawal, and food intake increased when cocaine was withdrawn. The results suggest that sensitive behavioral tests reveal aspects of drug dependence that may account for persistent abuse.

Animals↗
PubMed1987

Self-administration of orally-delivered phencyclidine and ethanol under concurrent fixed-ratio schedules in rhesus monkeys.

Five monkeys were trained to self-administer orally-delivered phencyclidine (0.25 mg/ml) and water under concurrent fixed-ratio 16 (FR 16) schedules during daily sessions that lasted 3 h. An 8% (w/v) ethanol solution was substituted for water and then the following series of phencyclidine concentrations was presented: 0.25, 0.5, 1, 0.03, 0.06, 0.12, 0 (water), and 0.25 mg/ml (retest). Next, the phencyclidine concentration was held constant (0.25 mg/ml), and the ethanol concentration was varied as follows: 8, 16, 32, 1, 2, 4, 0 (water), and 8% w/v (retest). Each drug concentration series was tested again with water concurrently available. At low phencyclidine concentrations the ethanol solution was preferred, but phencyclidine deliveries exceeded ethanol deliveries at higher phencyclidine concentrations. Ethanol-maintained responding was increased by the lower phencyclidine concentrations (0.03, 0.06 and 0.12 mg/ml), and it was slightly suppressed by the highest concentration (1 mg/ml). Phencyclidine was preferred to all concentrations of ethanol except 4%. Ethanol (8%) suppressed phencyclidine-maintained behavior at lower concentrations, but it had no effect at higher phencyclidine concentrations. The ethanol concentration-response functions were nearly identical whether phencyclidine (0.25 mg/ml) or water was concurrently present. Drug preferences were usually evident within the first 10 min of the session, suggesting they were based on olfaction, taste, or other immediate postingestional effects. These results show that two orally-delivered drugs may be concurrently self-administered under independently-operating FR schedules. Behavior maintained by one drug depends on the magnitude of the concurrently available, alternative reinforcing drug.

Administration, Oral↗
PubMed1987

Concurrent access to two concentrations of orally delivered phencyclidine: effects of feeding conditions.

Two experiments addressed the effects of food satiation and deprivation on oral self-administration of two concurrently available phencyclidine concentrations. In the first experiment, 8 rhesus monkeys self-administered either of two concentrations of phencyclidine ("PCP, angel dust") and water under concurrent fixed-ratio 16 schedules. One concentration was always held constant (0.25 mg/mL) while a series of other phencyclidine concentrations, ranging from 0 (water) to 1.0 mg/mL, was presented in a nonsystematic order. Initially the monkeys were tested while food satiated, and the procedure was then repeated during food deprivation. The monkeys usually selected the higher concentration within the first few minutes of the session, indicating that taste and/or other immediate postingestional effects were important factors. Contrary to a number of previous reports, there were no consistent differences across subjects in the mean number of liquid deliveries or mean drug intake (mg/kg) during food satiation and deprivation. However, for all monkeys the within-session time course of responding during food satiation consistently differed from that during deprivation. A second experiment assessed whether the failure to find consistent differences in drug intake during food satiation and deprivation had been due to the history of concurrent access to different phencyclidine concentrations or to the extended experience with phencyclidine under food-satiation conditions. Six additional monkeys (Group 2) were exposed to the phencyclidine self-administration procedure (during food satiation and deprivation) for the same length of time as the monkeys in Experiment 1 (Group 1), except they received only concurrent access to phencyclidine (0.25 mg/mL) and water. Both groups then received concurrent access to phencyclidine and water during five repeated cycles of food deprivation and satiation. There were also marked individual differences in Group 2: During food satiation, 2 of the monkeys' responding increased, 1 showed no change, and 3 decreased. Examination of a number of historical variables indicated that the greater the percentage of total sessions spent during food satiation with phencyclidine available (before these experiments began), the greater the amounts of phencyclidine consumed during food satiation and the smaller the differences in phencyclidine intake when the two feeding conditions were compared.

Animals↗
PubMed1987

A quantitative assessment of phencyclidine dependence produced by oral self-administration in rhesus monkeys.

Three rhesus monkeys were trained to self-administer orally delivered phencyclidine (PCP) and water under concurrent fixed-ratio schedules. Liquid deliveries were contingent upon lip-contact responses on solenoid-operated drinking spouts. PCP deliveries exceeded water deliveries throughout the experiment, indicating that the drug was functioning as a positive reinforcer. The monkeys were also trained to lever press under a fixed-ratio 64 or fixed-ratio 80 schedule of food delivery. Food was available during three 1 hr periods each day, with 6.5 hr of liquid availability between each food component. After behavior stabilized for at least 10 days under these conditions, water was substituted for PCP for 2, 4, 8 or 24 days. Food-maintained responding was severely disrupted for the first 2 days of water substitution, with a steady recovery over the following 6 days. The monkeys were noticeably irritable during water substitution, but there were no other physical signs of PCP withdrawal. Disruptions in food-maintained responding were immediately reversed when PCP was reinstated. Subsequently, the PCP concentration was varied (0.062, 0.125, 0.25, 0.5 and 1 mg/ml), and PCP intake (milligrams per kilogram), as well as the magnitude of disruptions in pellet deliveries (upon termination of PCP access), also varied directly with PCP intake. The amount of PCP intake was also altered by limiting PCP (0.25 mg/ml) access to every 2nd or 4th day, with water available on intervening days. Pellet deliveries were substantially disrupted during water substitution, and food-maintained responding immediately returned to control levels when PCP became available.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1986

Food deprivation reveals strain differences in opiate intake of Sprague-Dawley and Wistar rats.

Two groups of naive, male, albino rats derived from different genetic strains (Sprague-Dawley and Wistar) were given a 5 micrograms/ml etonitazene solution as their only available liquid. Liquid intake and body weights were recorded every 24 hr. Etonitazene intake was compared to baseline water intake, and drug intake was then compared when the rats were food deprived (25 sessions) and food satiated (24 sessions). Both groups drank similar amounts of water and etonitazene during the initial food satiation phase, although drug intake was slightly below water intake. When they were food deprived, the Wistar group's mean etonitazene intake almost doubled, while the Sprague-Dawley group's drug intake decreased by nearly 50%. The etonitazene intake in the Sprague-Dawley group never exceeded that of the vehicle, water; thus, it appeared that the drug was not functioning as a reinforcer. Food deprivation increased etonitazene intake above water levels in the Wistar group, indicating that the drug was serving as a reinforcer. Both groups showed similar drug effects during food deprivation, such as erratic drinking patterns, self-mutilation and other forms of stereotypy. Thus, both strains were sensitive to etonitazene's effects; they appeared to differ only with respect to the reinforcing effects. These results suggest that genetically-based differences in the reinforcing effects of drugs may be revealed by food deprivation.

Animals↗
PubMed1986

Effects of naltrexone on intravenous cocaine self-administration in rats during food satiation and deprivation.

Rats self-administered i.v. delivered cocaine (0.1 mg/kg) under conditions of continuous access (session length 24 hr). Each lever press resulted in an infusion according to a fixed-ratio 1 schedule. Food was continuously available except for every third session, when the rats were food deprived, i.e., provided with only 8 g at the start of the session. After behavior stabilized, the rats were given naltrexone (N), saline (V) or no injections (O) on successive days according to the following sequence: N, V, O, V, N, O. . . . This sequence began on a food deprivation session and repeated until four naltrexone and four saline injections had been given during both food satiation and deprivation sessions, although data were reported from only the last three sessions under each condition. Injections were given at the start of the session and after 7 hr of the session had elapsed. Cocaine was then replaced by saline for approximately half the rats, and the entire injection sequence was repeated until three naltrexone and three saline pretreatment sessions were completed during both food satiation and deprivation. Three separate groups of 9 or 10 rats each received a different dose of naltrexone (0.5, 1 or 2 mg/kg i.v.). As reported earlier, cocaine- and saline-reinforced responding increased more than 2-fold during food deprivation. During food satiation, naltrexone pretreatment nearly doubled cocaine self-administration, with the greatest increase at the 1-mg/kg naltrexone dose. Naltrexone had no systematic effect on cocaine-reinforced responding during food deprivation, and it had no effect on saline-maintained responding during food satiation or deprivation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

The role of food deprivation in the maintenance and reinstatement of cocaine-seeking behavior in rats.

Lever-pressing responses of a group of five rats (Group E) were rewarded with i.v. injections of cocaine (0.1 mg/kg) under conditions of continuous access for eleven 24-h sessions. When the rats were partially food-deprived every third day, cocaine infusions more than doubled during that session. When saline was substituted for cocaine, responding diminished over a 10-day period (Extinction Phase), but when the rats were subsequently food-deprived every third day (Testing Phase), for a total of six cycles (20 sessions), high rates of responding for saline were reinstated only during food deprivation sessions. Seven control groups were included to investigate several questions regarding this effect. Group C-1 received cocaine but no food deprivation experience during the Training Phase, and Group C-2 received food deprivation experience without cocaine access. The results showed that simultaneous presentation of both the food deprivation condition and cocaine was necessary to reinstate food deprivation-induced increases in responding during the Testing Phase. To test for the importance of the contingency between responding and cocaine infusions during food deprivation (and satiation) in the Training phase, Group C-3 was yoked to Group E; they received the same number and pattern of infusions during the Training Phase, but infusions were not contingent upon lever-press responses. This group showed only small increases in saline-maintained responding due to food deprivation during the Testing Phase. Groups C-4 and C-5 were treated as Groups C-3 and E, respectively, except they were partially food-deprived during the 10-day Extinction Phase. Three of five rats in Group C-4 and all rats in Group C-5 showed no increases due to food deprivation during the Testing Phase. Group C-6 was pre-exposed to food deprivation before the experiment began, and Group C-7 was exposed to food deprivation only once during the Training Phase. Both procedures weakened the ability of food deprivation to produce high rates of saline-maintained responding. It was concluded that novel interoceptive stimuli related to food deprivation had become associated with the relatively novel reinforcing effects of cocaine and these interoceptive stimuli functioned as conditioned reinforcers to increase the maintenance and reinstatement of drug-seeking behavior.

Animals↗