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Biomedical subjects

M E Carroll

Publications and source records attributed to M E Carroll.

At least 37 records · Page 2Linked to original sources
PubMed1999

The effects of restraint stress on voluntary ethanol consumption in rats.

Sixty Wistar rats (Rattus norvegicus) were assigned to 4 groups of 15 rats each: ethanol stress (ES), ethanol no-stress (EN), isocaloric stress (IS) and isocaloric no-stress (IN). The effect of restraint stress on daily intake of ethanol and a 0.72% solution of glucose was examined in an ABA design (stress-no stress-stress). During the stress phases, 2 groups were subjected to daily 15-min restraint stress, whereas 2 groups were placed in different cages for 15 min as a control. All 4 groups were then given 6-hr access to their assigned liquid alone for 4 days followed by a choice between their assigned liquid and water on the 5th day. The ES group significantly increased their ethanol intake (g/kg) compared to the EN group on choice days but not on forced days. Percentage preference for ethanol was significantly greater and increased at a faster rate over the 75-day testing period compared with the EN group. However, total ethanol consumption (g/kg) and percentage preference did not vary as a function of phase. It is notable that the effects of restraint stress on ethanol self-administration persisted even after the stress schedule was removed.

Alcohol Drinking↗
PubMed1998

Dietary additives and the acquisition of cocaine self-administration in rats.

The effects of dietary caffeine and the amount and palatability of food on the acquisition of cocaine (0.2 mg/kg) self-administration were examined. Using an autoshaping procedure, seven groups of 13 rats each were trained to press a lever resulting in a cocaine (0.2 mg/kg infusion under a fixed-ratio 1 (FR 1) schedule. One group had ad libitum access to caffeine- (0.2% w/w) admixed food. Three groups had access to 10 g, 20 g or ad lib food each day. Another three groups had the same three amounts of ground food with powdered saccharin (0.2% w/w) added. During daily 6-h autoshaping sessions, ten infusions were delivered each hour under a random-time 90-s schedule after a brief (15 s) extension of a retractable lever. These were followed by 6-h self-administration sessions, when the lever remained extended and cocaine infusions were available under an FR 1 schedule. The acquisition criterion was self-administration of a mean of 100 infusions over 5 days. Cocaine self-administration was accelerated in the caffeine group compared to the regular chow group. However, by 30 days nearly the same percentage of rats in the caffeine and regular food groups met the acquisition criterion. In the other six groups, as the amount of food increased, the rate of acquisition and percentage of rats per group meeting the acquisition criterion decreased. In the ad lib group, acquisition was further reduced when saccharin was added to food. In summary, dietary caffeine accelerated acquisition and a greater amount and increased palatability of food independently interfered with acquisition of cocaine self-administration in rats.

Animals↗
PubMed1998

Acquisition of oral phencyclidine (PCP) self-administration in rhesus monkeys: effects of dose and an alternative non-drug reinforcer.

The effects of drug dose and a non-drug alternative reinforcer on acquisition of oral PCP self-administration in rhesus monkeys were examined. Acquisition was studied using three groups of monkeys (seven subjects per group). One group received a low PCP dose (0.0375 mg/delivery) and the other two received a high PCP dose (0.15 mg/delivery). One of the high dose groups had concurrent access to a saccharin solution (0.03% w/v) and water during the intersession (17.5-h) period. Food non-restricted monkeys were initially given access to water under a fixed-ratio (FR) 1 schedule during daily 3-h sessions. Water was then replaced with PCP during the session. The monkeys were then reduced to 85% of their free-feeding body weights and fed before the session, and the FR value was increased from 1 to 2, 4 and 8. Subsequently, food was given post-session and water and PCP were available under concurrent FR 8 schedules. At this final step of the procedure, acquisition of PCP self-administration was considered to occur if PCP intake consistently exceeded water intake. When all three groups were given concurrent access to PCP and water, PCP intake was greater than water intake only in the group of monkeys receiving the high PCP dose. PCP intake increased when water replaced saccharin during intersession in the high PCP dose group. Within-group data revealed that 85.7% of monkeys acquired PCP reinforcement in the group given access to the high PCP dose while only 42.8% acquired in the other two groups. These data suggest that drug dose and presence of alternative non-drug reinforcers affect acquisition of drug self administration in non-human primates.

Administration, Oral↗
PubMed1998

A novel paradigm to investigate regulation of drug intake in rats self-administering cocaine or heroin intravenously.

The purpose of this experiment was to investigate the regulation of drug intake in rats (n = 20) self-administering heroin or cocaine during daily 5-hr sessions. Operant chambers were equipped with 2 levers and associated stimulus lights. A response on the lever with stimuli signaling an increase in dose size increased the infusion duration by 3 s, and a response on the lever with stimuli signaling a decrease in dose size decreased the infusion duration by 3 s. Results showed that daily and hourly drug intake for cocaine and heroin groups were relatively constant. Significant correlation coefficients were obtained for heroin and cocaine groups for the relationship between interdose interval (IDI) and infusion duration (dose size). These findings indicate that subjects regulated their drug intake by adjusting IDI throughout drug self-administration sessions.

Animals↗
PubMed1998

Effects of amphetamine, butorphanol, and morphine pretreatment on the maintenance and reinstatement of cocaine-reinforced responding.

Three groups of rats (N = 23) self-administered intravenous cocaine (0.4 mg/kg/infusion) during the initial 2 hr of daily 7-hr sessions. During the remaining 5 hr of these sessions, responding produced saline infusions. On test days, each rat was pretreated with an assigned dose of either butorphanol, morphine, amphetamine, or saline before the self-administration session followed by a priming injection of cocaine (3.2 mg/kg i.v.) or saline at the beginning of the 4th hr. Results showed that both amphetamine (0.5, 1.0, and 2.0 mg/kg) and morphine (0.3, 1.0, and 2.0 mg/kg) pretreatment dose-dependently reduced cocaine self-administration whereas only amphetamine affected (increased) reinstatement responding. Butorphanol pretreatment (8 mg/kg) suppressed cocaine self-administration and blocked the effect of the cocaine priming injections on pretreatment testing days. These findings indicate that (a) pretreatment drugs with similar stimulus properties potentiate reinstatement of responding and (b) pretreatment drugs can differentially affect maintenance and reinstatement of responding.

Amphetamine↗
PubMed1998

Ethanol consumption in rats when dose size is under subject control.

Rats orally self-administered ethanol when they could control dose size as follows: A lever press initiated a trial; a press on 1 lever increased the previous trial duration by 30% whereas a press on a 2nd lever decreased the previous trial duration by 30%. During a trial, rats could drink either water, 8%, or 16% (wt/vol) ethanol (ETOH) from a lick-sensitive fountain. Mean per session intake of 8% and 16% ETOH was 0.8 g/kg and 1.3 g/kg, respectively. Water intake was negligible. Rats did not show a tendency to maintain a particular trial duration, nor did they adjust intertrial intervals to previous dose size (number of licks). When trials were collected into bouts, a positive relationship was found between bout size and interbout interval; this relationship was statistically significant for the 8% but not the 16% ETOH condition.

Alcohol Drinking↗
PubMed1998

Caffeine withdrawal in normal school-age children.

OBJECTIVE: Caffeine is widely consumed by children around the world. The purpose of this study was to determine whether children manifest withdrawal effects after cessation of caffeine intake. METHOD: Thirty normal children completed the single-blind, within-subjects, repeated-measures study with weekly sessions. Subjects were tested four times: (1) baseline (on regular caffeine diet); (2) on caffeine (approximately 120 to 145 mg/day); (3) during withdrawal (24 hours after discontinuation of caffeine taken for 13 consecutive days); and (4) at return to baseline. Subjects were evaluated with self-report measures of symptoms and objective measures of attention, motor performance, processing speed, and memory. RESULTS: During caffeine withdrawal, there was a significant deterioration on response time of a visual continuous performance test of attention. This finding is consistent with caffeine withdrawal. The deterioration in response time appeared to persist for 1 week. CONCLUSIONS: Twenty-four hours after children discontinued caffeine, there was a decrease in performance on reaction time of a task requiring sustained attention. Further work is indicated to determine whether children manifest caffeine withdrawal effects after cessation of caffeine intake.

Analysis of Variance↗
PubMed1997

Effects of buprenorphine and an alternative nondrug reinforcer, alone and in combination on smoked cocaine self-administration in monkeys.

The abuse of smoked cocaine base, also known as 'crack', continues to be a major public health problem and to date the success of pharmacological or behavioral interventions has been limited. The purpose of this study was to evaluate the efficacy of a behavioral (alternative reinforcer-saccharin) and pharmacological (0.01 mg/kg buprenorphine) treatment alone and in combination. Five adult male rhesus monkeys self-administered cocaine base (1.0 mg/kg/delivery) via the smoking/inhalation route. Each day ten smoke deliveries were available contingent upon completion of a chained FR (lever press), FR (inhalation response) response schedule during 4 hr sessions. The data were analyzed using a behavioral economic framework in which the lever press response requirements were varied from 64 to 1024 to generate a demand function (consumption x FR) for cocaine under the following conditions: (1) buprenorphine pretreatment alone (0.01 mg/kg, i.m., 30 min presession); (2) concurrent access to saccharin alone (0.03% wt/vol); and (3) buprenorphine pretreatment in the presence of concurrent access to saccharin. Under all conditions, increases in the lever FR resulted in significant decreases in smoked cocaine base deliveries. Neither buprenorphine pretreatment alone nor concurrent saccharin alone produced significant decreases in smoked cocaine deliveries; however, the combination of buprenorphine pretreatment and concurrent saccharin significantly decreased the mean number of smoked cocaine deliveries from the no treatment baseline and from the buprenorphine alone condition. These data suggest that the combination of pharmacotherapy and alternative reinforcers may be an effective treatment strategy to alter smoked cocaine self-administration.

Animals↗
PubMed1997

Acquisition of i.v. amphetamine and cocaine self-administration in rats as a function of dose.

The effect of dose on the acquisition of i.v. amphetamine and cocaine self-administration was examined. Three unit doses of amphetamine (0.03, 0.06 and 0.12 mg/kg) and three unit doses of cocaine (0.05, 0.2 and 0.8 mg/kg) were tested in separate groups of ten (amphetamine) or 13 (cocaine) rats. Autoshaping methods were used to train rats to press a lever that resulted in drug infusion under a fixed-ratio (FR) 1 schedule. A daily 6-h autoshaping component non-contingently delivered 60 infusions according to a 60-s random time schedule with ten infusions delivered during the first half of each h. Each day autoshaping sessions were followed by a 6-h self-administration session. The criterion for acquisition was a 5-day period during which a daily mean of 100, 50 or 25 infusions for the three amphetamine doses and 400, 100 or 25 infusions were earned during the 6-h self-administration period for the three cocaine doses, respectively. As dose increased, more rats per group acquired drug self-administration and the mean number of days to meet the acquisition criterion decreased. The percentage of rats acquiring amphetamine self-administration increased with dose and ranged from 80 to 100%. Only one rat at the lowest cocaine dose met the acquisition criterion, but 100 percent of the rats at the two higher doses acquired. During the last 2 days of acquisition, mean infusions decreased and mean drug intake (mg/kg) increased as dose increased. On the last day of acquisition, the time course of infusions during the 6-h self-administration component was characterized by a steady rate of infusions per hour, and number of infusions was inversely related to dose. These findings indicate that the initial available dose of a drug is an important determinant of the rate and probability that successful acquisition will occur.

Animals↗
PubMed1997

A comparison of progressive ratio schedules versus behavioral economic measures: effect of an alternative reinforcer on the reinforcing efficacy of phencyclidine.

Alternative non-drug reinforcers have been demonstrated to decrease drug-reinforced behavior by both decreasing relative reinforcing efficacy and substituting for the drug reinforcer. The effect of saccharin on responding maintained by orally delivered phencyclidine (PCP) was examined in this study using concurrent progressive-ratio (PR) schedules of reinforcement and a behavioral economic analysis of demand. Seven adult male rhesus monkeys self-administered PCP (0.06, 0.12, 0.25, 0.50 and 1.0 mg/ml) and either concurrent water or saccharin (0.03% wt/vol) from two drinking spouts under concurrent independent PR schedules. During daily sessions the response requirements (lip contacts on automatic drinking spouts) increased across 15 levels, from 8 to 4096. Each successful ratio completion resulted in the availability of 40 liquid deliveries under an FR 1 schedule and a subsequent increment in the PR. Concentrations of PCP were presented in a non-systematic order and presentation of the concurrent liquid, saccharin or water, was counterbalanced across subjects. All behaviors maintained by PCP were significantly greater than those maintained by water. Replacement of water with saccharin served to significantly decrease PCP-maintained responding and break points (BP) across the range of PCP concentrations; however, saccharin did not significantly decrease deliveries of PCP. Saccharin maintained significantly greater responding, BPs and deliveries compared to either PCP or water, across all PCP concentrations. The use of BP as a measure of reinforcing efficacy suggests that saccharin decreased the relative reinforcing efficacy of PCP. Furthermore, behavioral economic analyses suggested that saccharin decreased maximal PCP-maintained responding (Pmax) in a similar fashion, suggesting that BP and Pmax may be analogous measures of reinforcing efficacy.

Animals↗
PubMed1997

Smoked heroin and cocaine base (speedball) combinations in rhesus monkeys.

The purpose of this investigation was to compare the self-administration of heroin and cocaine base, alone and in combination, in rhesus monkeys (Macaca mulatta) self-administering a combination of heroin (0.1 mg/kg/delivery) and cocaine base (1.0 mg/kg/delivery) via the smoking route. Smoke deliveries were contingent on completion of a chained fixed ratio (FR; lever press), FR 5 (inhalation) schedule. The lever press FR values (64, 128, 256, 512, and 1024) represented increasing drug price. Demand functions (Consumption X price) were obtained for the heroin and cocaine combination and compared with previously determined demand functions for smoked heroin and cocaine alone. As the FR increased and the number of responses emitted increased, the number of drug deliveries decreased. The demand functions were not different for heroin versus cocaine alone or for the cocaine alone versus the cocaine-heroin combination. However, the demand for heroin alone was significantly less than the demand for the cocaine-heroin combination, suggesting that smoked cocaine base enhances the behavioral effects of smoked heroin.

Administration, Inhalation↗
PubMed1996

Combined effects of buprenorphine and a nondrug alternative reinforcer on i.v. cocaine self-administration in rats maintained under FR schedules.

Although previous studies have shown that pharmacological agents, such as buprenorphine, and alternative nondrug reinforcers, such as money or sweetened solutions, reduce cocaine self-administration, few studies have examined the combined effects of these two approaches. The purpose of the present study was to evaluate the effects of the opioid partial against buprenorphine (0.1 mg/kg) and concurrent access to either water or a glucose plus saccharin solution (G+S, 3% and 0.125% wt/vol) in rats self-administering intravenous (IV) cocaine (0.4 mg/kg per infusion) under fixed-ratio schedules (FR2, 8 or 32). One group had concurrent access to water and another group had concurrent access to G+S. After 3 consecutive days of stable cocaine self-administration, a single buprenorphine injection (0.1 mg/kg IV) was administered 30 min before the start of the experimental session for 3 consecutive days. To summarize the results, (1) the presence of an alternative non-drug reinforcer significantly reduced cocaine self-administration, (2) buprenorphine selectively decreased cocaine, but not water or G+S, self-administration; (3) the decrease in cocaine infusions by buprenorphine was greatest on the first day of buprenorphine administration; and (4) expressed as a percentage of baseline conditions, the combination of buprenorphine and G+S produced a greater decrease in cocaine self-administration than either buprenorphine or G+S alone. These results indicate that combined treatment with buprenorphine and concurrent access to a sweetened solution is a more effective strategy for reducing cocaine self-administration than either strategy alone.

Animals↗
PubMed1996

Smoked heroin self-administration in rhesus monkeys.

The purpose of the present study was to evaluate behavioral and pharmacological determinants of smoked heroin self-administration. Eight rhesus monkeys were trained to self-administer smoked heroin under a chained fixed-ratio, (FR, 64-1024) for lever presses, FR 5 for inhalations schedule during daily experimental sessions. Demand for heroin was determined by plotting consumption (smoke deliveries) as a function of price which was varied by increasing the FR lever press requirement from 64 to 1024. The heroin demand curve was compared to that obtained with smoked cocaine base. Dose-effect determinations were obtained by varying the unit dose of heroin from 0.025 to 1.6 mg/kg per delivery. Pretreatment with naloxone (0.01-1.0 mg/kg IM, 10 min presession) and substitution tests with the peripherally acting opioid loperamide (0.1 mg/kg per delivery) were also conducted. Deliveries of smoked heroin decreased, but lever responding per delivery increased as the FR increased. Demand for heroin was elastic and comparable to demand for smoked cocaine base. Varying the dose of heroin available for self-administration resulted in an asymptotic dose-effect curve. Naloxone pretreatment produced dose-dependent decreases in heroin self-administration. Substitution of loperamide for heroin produced extinction-like responding within one or two sessions, with the total smoke deliveries decreasing by 80% of heroin levels within 8-15 days. Reinstatement of heroin resulted in a rapid return to baseline levels of self-administration. These data suggest that rhesus monkeys will readily and reliably self-administer heroin via the inhalation route, and behavioral and pharmacological manipulations indicate that smoked heroin functioned as a positive reinforcer.

Animals↗
PubMed1996

Oral caffeine pretreatment produced modest increases in smoked cocaine self-administration in rhesus monkeys.

Several recent studies have shown that caffeine potentiates the reinforcing, discriminative stimulus, and motor activating effects of cocaine in rats. The present study was designed to determine whether oral caffeine pretreatment would enhance the reinforcing effects of cocaine in rhesus monkeys trained to self-administer smoked cocaine base. The effects of oral caffeine pre-treatment (0, 100, or 200 mg) and fixed-ratio (FR) value on cocaine-base smoking were evaluated in four male rhesus monkeys. Monkeys responded on a lever under a fixed-ratio (FR) schedule (FR 128, 256, 512, 1024, 2048, or 4096) and then made five inhalations on a smoking spout to gain access to volatilized cocaine base (0.25 or 1.0 mg/kg per delivery) during daily experimental sessions. Twenty pellets [20 non-caffeinated (0 mg caffeine), ten non-caffeinated+ten caffeinated (100 mg caffeine), or 20 caffeinated (200 mg caffeine) pellets] were administered 30 min prior to experimental sessions. The lever FR value was held constant within each experimental session, but was increased after 3 consecutive days of stable responding. Although the number of smoke deliveries that was self-administered significantly decreased from FR 128 to FR 4096, it did not change as a function of cocaine dose across the range of FR values tested. However, the interaction between cocaine dose and caffeine pretreatment was statistically significant. Compared to 0 mg caffeine, three of four monkeys pretreated with 200 mg caffeine responded for a greater number of smoke deliveries when they were maintained on a cocaine dose of 1.0 mg/kg per delivery, but not 0.25 mg/kg per delivery. Thus, caffeine pretreatment can produce small, but statistically significant increases in smoked cocaine self-administration in rhesus monkeys.

Administration, Oral↗
PubMed1996

Progressive ratio and behavioral economic evaluation of the reinforcing efficacy of orally delivered phencyclidine and ethanol in monkeys: effects of feeding conditions.

The effect of feeding conditions on the reinforcing efficacy of orally-delivered drugs was evaluated using a progressive-ratio (PR) paradigm and a behavioral economic analysis of demand. Seven monkeys self-administered phencyclidine (PCP) (0.06, 0.12, 0.25, 0.5, and 1.0 mg/ml) or ethanol (2, 4, 8, 16, and 32% wt/vol) and concurrent water from two drinking spouts under concurrent PR schedules. The ratios increased from 8 to 4096, and 40 liquid deliveries were available after completion of each ratio schedule. The entire range of drug concentrations was presented in nonsystematic order under two feeding conditions, food restriction and food satiation. Drug maintained responses, deliveries and break points were significantly greater than those maintained by water. Food restriction significantly increased the rate of PCP-maintained responses, deliveries and PR break points over the food satiation baseline. There was also a significant interaction between feeding condition and drug concentration. Although ethanol-maintained responses, liquid deliveries and break points consistently increased in five of seven monkeys during food restriction, only drug concentration produced significant differences in these measures. Using break point as a measure of reinforcing efficacy, food restriction increased the reinforcing efficacy of PCP and had a more pronounced effect at higher drug unit prices.

Administration, Oral↗
PubMed1996

The relationships among saccharin consumption, oral ethanol, and i.v. cocaine self-administration.

The purpose of the present experiment was to replicate previously reported observations of a relationship between saccharin consumption and oral ethanol self-administration in rats using operant measures (2,8) and to determine whether saccharin intake was related to the rate of acquisition of IV cocaine self-administration. Groups of Wistar rats selected for high and low saccharin (0.1% wt/vol) intake were tested for rate of acquisition of IV cocaine (0.2 mg/kg/infusion) self-administration using an autoshaping procedure. They were subsequently tested for self-administration of oral ethanol (8% wt/vol) under ascending fixed-ratio (FR) schedules (FR 1, 2, 4, and 8). Finally, ethanol deliveries were compared under food-deprivation and food-satiation conditions under an FR 8 schedule. Saccharin intake was redetermined after each phase of the experiment. No significant differences between high and low saccharin groups were found in rate of acquisition of IV cocaine self-administration, and there was not a significant correlation between saccharin and cocaine consumption. However, the high saccharin group drank significantly more ethanol than the low saccharin group during the FR 8 food satiation component. A significant correlation between saccharin and ethanol consumption was also found. For high and low saccharin groups, responding for ethanol increased proportionally with increases in FR such that consumption of ethanol remained relatively constant as FR increased. Ethanol consumption was significantly increased under food deprivation relative to food satiation conditions for both saccharin groups. A significant correlation between ethanol consumption and cocaine consumption was also found. Significant increases in saccharin consumption across successive saccharin consumption tests were found for both groups, although relative intake for the high and low saccharin groups remained stable throughout the experiment. These results indicate that higher ethanol intake is predicted by higher saccharin intake, but saccharin intake did not predict the rate of acquisition of IV cocaine self-administration.

Alcohol Drinking↗
PubMed1995

Food deprivation affects extinction and reinstatement of responding in rats.

Food deprivation has been shown to increase the self-administration of a wide variety of drugs in a number of different species. However, the effects of food deprivation on other phases of drug taking have not been established. The purpose of the present study was to evaluate the effects of food deprivation on reinstatement of responding for cocaine. Rats trained to self-administer 0.2, 0.4, or 1.0 mg/kg cocaine intravenously (IV) under a fixed-ratio 1 schedule for the first 2 h during daily 7-h sessions were fed either before or after the experimental session. During hours 3-7, rats self-administered saline. Saline replaced cocaine in the infusion pumps at the beginning of hour 3 and a priming injection of either saline or cocaine (0.32, 1.0, or 3.2 mg/kg IV) was administered at the beginning of hour 4. The number of infusions that was self-administered was measured throughout the 7-h session. During hours 1 and 2 when cocaine was available, the number of infusions was inversely related to cocaine dose. During hour 3, rats typically self-administered several infusions of saline, which gradually decreased to near-zero levels by hours 4-7 (extinction responding). A priming injection of cocaine administered at the beginning of hour 4 reinstated responding in a dose-related manner. The magnitude of extinction responding during hour 3 and reinstatement of responding during hour 4 were similar regardless of cocaine maintenance dose.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗