Access Scheduling Research Articles

Salvia miltiorrhiza Extract Inhibits Alcohol Absorption, Preference, and Discrimination in sP Rats

Experiment 1 of the present study investigated the ability of a standardized extract of Salvia miltiorrhiza in reducing voluntary ethanol intake in ethanol-preferring rats of the sP line. Ethanol intake occurred under the two-bottle free-choice regimen between 10% (v/v) ethanol and water in daily 4-h scheduled access periods; water was present 24 h/day. Intragastric administration of 200 mg/kg Salvia miltiorrhiza extract resulted in approximately 40% reduction in ethanol intake and preference throughout the 4-day treatment. This effect of Salvia miltiorrhiza extract was likely due to its ability of altering ethanol absorption from the gastrointestinal tract. Indeed, Experiments 2 and 3 of this study demonstrated that 200 mg/kg Salvia miltiorrhiza extract reduced blood ethanol levels (BELs) up to 60% in comparison to control rats, when ethanol was given IG, whereas it failed to modify BELs when ethanol was injected IP. The reducing effect of Salvia miltiorrhiza extract on ethanol absorption may have therefore resulted in an attenuated perception of the psychoactive effects of ethanol sought by ethanol-drinking rats. Consistently, the results of Experiment 4 of the present study demonstrated that a combination of 200 mg/kg Salvia miltiorrhiza extract IG and 1 or 2 g/kg ethanol IG resulted in a partial blockade of the discriminative stimulus effects of ethanol in sP rats trained to discriminate these doses of ethanol from water in a drug discrimination procedure. Collectively, the results are discussed as being suggestive that drugs curbing ethanol absorption from the gastrointestinal tract may constitute a novel strategy for controlling excessive alcohol consumption in human alcoholics.

Limited Access to a Dietary Fat Option Affects Ingestive Behavior But Not Body Composition in Male Rats

Restricting access to high-fat foods is a common strategy utilized to promote health. This strategy may contribute to episodes of overconsumption, however, when the restricted foods subsequently become available. The present study utilized a rat feeding procedure to determine if restricting access to an optional source of dietary fat would increase later consumption of that food under nonenergy-deprived conditions. Five groups of male Sprague–Dawley rats were used, all of which had continuous access to a standard rodent diet and water. The control group had no access to shortening. The low-restriction group had 2-h access to shortening every day. The high-restriction group had 2-h access to shortening on Monday, Wednesday, and Friday. Two additional groups were switched between the high and low conditions. Two-hour and 24-h food intakes were measured every day for 6 weeks. At the end of the study rats were sacrificed and carcass composition determined. As access to the shortening decreased, consumption during the 2-h access period increased. Rats compensated for the increased shortening consumption by decreasing intake of the standard diet. Thus, cumulative energy consumption did not differ among the groups. When switched between the high and low conditions, rats rapidly adjusted to the change in shortening availability. There were no effects of access schedule on carcass composition. These results indicate that restricting access to an optional high-fat food, even under nonenergy-deprived conditions, can promote significant increases in the consumption of that food when it subsequently becomes available.

A modular algorithm for resource allocation

This paper concerns resource allocation in distributed message passing systems, i.e., the scheduling of accesses to exclusive system resources shared among concurrent processes. An efficient modula...

Serotonin 3 Receptor Antagonism of Alcohol Intake: Effects of Drinking Conditions

M cKINZIE, D. L., R. EHA, R. COX, R. B. STEWART, W. DYR, J. M. MURPHY, W. J. M cBRIDE, L. LUMENGAND T.-K. LI. Serotonin 3 receptor antagonism of alcohol intake: Effects of drinking conditions. ALCOHOL 15(4) 291–298, 1998.—The effects of 5-HT 3 receptor antagonists on ethanol intake were examined in the selectively bred alcohol-preferring P line of rats under continuous and limited access to 10% (v/v) ethanol with food and water ad lib. Single daily injections of either MDL 72222 (MDL) or ICS 205-930 (ICS) (0.01–3.0 mg/kg, SC) given 60 min before a 4-h scheduled access period for 4 consecutive days failed at all doses to alter the intake of a 10% (v/v) ethanol solution by P rats. However, multiple daily injections of either MDL (1–3 mg/kg, SC) or ICS (3.0 and 5.0 mg/kg, SC), given three times daily at 4-h intervals, significantly reduced ethanol intake under 24-h free-choice conditions on the first treatment day. Additionally, a single administration of 1.0 mg/kg MDL reduced 24-h free-choice ethanol intake by approximately 50% of control values and had no effect on 24-h saccharin intake. The effects of MDL were further examined in a 2-h schedule access paradigm in which rats received the access period at the same time every day (Fixed) or randomly during the dark cycle (Variable). Although 1.0 mg/kg MDL had little effect on ethanol drinking in the Fixed group, ethanol intake was reduced by 55% of control levels in the Variable group. Overall, the data indicate that drinking conditions influence the effectiveness of 5-HT 3 antagonists to reduce ethanol consumption. Furthermore, the results suggest that conditions, associated with limited access ethanol drinking, markedly reduce the actions of 5-HT 3 antagonists on ethanol intake.

Reduction of voluntary ethanol intake in ethanol-preferring sP rats by the cannabinoid antagonist SR-141716.

The present study assessed the efficacy of the cannabinoid CB1 receptor antagonist, SR-141716, in reducing voluntary ethanol intake in selectively bred Sardinian alcohol-preferring (sP) rats. Ethanol (10%, v/v) and food were available in daily 4 h scheduled access periods; water was present 24 h/day. The acute administration of a 2.5 and a 5 mg/kg dose of SR-141716 selectively reduced ethanol intake, whereas a 10 mg/kg dose of SR-141716 reduced to a similar extent both ethanol and food intake. These results suggest that the cannabinoid CB1 receptor is involved in the mediation of the ethanol-reinforcing effects in sP rats.

Naltrexone Treatment Increases the Aversiveness of Alcohol for Outbred Rats

Acute naltrexone treatments (0.0, 0.5, 1., or 3.0 mg/kg body weight) were administered to separate groups of rats and alcohol taste reactivity and consumption were measured. Rats were given daily naltrexone injections and then tested for taste reactivity to 10% alcohol 30 and 60 min after injection. Each reactivity trial (total of 4) was 60 sec during which 1 ml of fluid was infused. The rats' orofacial and body movements were videotaped and scored later. In the final measure, rats were placed on a restricted fluid access schedule and given naltrexone treatments 10 min before being presented with the 10% alcohol solution in the home case (60-min drinking period). After 4 days of consumption tests under the drug condition, the rats were given 4 more daily tests without the drug. Results indicated that the two highest naltrexone doses significantly decreased ingestive responding and increased aversive responding, particularly at the 30-min test. Both the 1.0 and 3.0 mg/kg body weight doses also significantly decreased alcohol consumption as measured during the free access tests. Alcohol consumption returned to control levels immediately after the drug treatments were stopped. The data show that dosages of naltrexone 1.0 mg or higher significantly alter both alcohol taste reactivity (increased aversiveness and decreased palatability) and alcohol consumption (decreased intake) in outbred rats. These results are discussed in relation to naltrexone treatment as a means for decreasing alcohol use and abuse.

Effects of dopaminergic drugs on food- and cocaine-maintained responding. IV: continuous cocaine infusions

The effects of cocaine (continuously infused during the session with and without a pre-loading dose) on responding maintained under multiple fixed-ratio 30 schedules of limited access to food and cocaine delivery (10 or 56 μg/kg per injection) were studied in nine rhesus monkeys. When responding was maintained by 10 μg/kg per injection, cocaine decreased rates of cocaine-maintained responding in a dose-related manner while having no effect on food-maintained responding. When responding was maintained by 56 μg/kg per injection, cocaine decreased both cocaine- and food-maintained responding. These results show that the effects of continuous infusions of cocaine depend upon both the unit dose of cocaine and the event that maintains responding. As such, the effects of continuous infusions of cocaine are similar to those of other, longer-acting dopamine agonists. Such results support the development of long-acting agonist approaches to the pharmacotherapeutic treatment of cocaine abuse.

Thyrotropin Releasing Hormone Analog TA‐0910 Suppresses Alcohol Intake in Alcohol Drinking African Green Monkeys

In previous studies, we found that single injections of the thyrotropin-releasing hormone analog TA-0910 dose-dependently reduced alcohol intake and preference in alcohol-preferring (P) and Fawn-Hooded (FH) rats over a 24-hr period of continuous access to alcohol and water. However, several consecutive daily injections of TA-0910 resulted in the development of tolerance to these effects. In the present study, we found that in a 5-hr limited-access schedule in which monkeys could select an aqueous alcohol solution (7.5% v/v) or tap water, single doses of TA-0910 (0.0625, 0.125, 0.25, 0.5, and 0.75 mg/kg), similar to those found effective in P and FH rats, reduced consumption of alcohol. In this protocol, tolerance to the attenuating effects of TA-0910 on alcohol intake was not evident after five consecutive once-daily doses of 0.5 mg/kg. Furthermore, it was shown that a single dose of 0.75 mg/kg TA-0910 did not significantly influence 24-hr water intake when water was the only available fluid, but did reduce the intake of a preferred solution of saccharin. These findings suggest that activation of brain thyrotropin-releasing hormone systems reduces alcohol intake in primates and that tolerance to this effect is not evident within 5 days under a limited access schedule.

Thyrotropin Releasing Hormone Analog TA-0910 Suppresses Alcohol Intake in Alcohol Drinking African Green Monkeys

In previous studies, we found that single injections of the thyrotropin-releasing hormone analog TA-0910 dose-dependently reduced alcohol intake and preference in alcohol-preferring (P) and Fawn-Hooded (FH) rats over a 24-hr period of continuous access to alcohol and water. However, several consecutive daily injections of TA-0910 resulted in the development of tolerance to these effects. In the present study, we found that in a 5-hr limited-access schedule in which monkeys could select an aqueous alcohol solution (7.5% v/v) or tap water, single doses of TA-0910 (0.0625, 0.125, 0.25, 0.5, and 0.75 mg/kg), similar to those found effective in P and FH rats, reduced consumption of alcohol. In this protocol, tolerance to the attenuating effects of TA-0910 on alcohol intake was not evident after five consecutive once-daily doses of 0.5 mg/kg. Furthermore, it was shown that a single dose of 0.75 mg/kg TA-0910 did not significantly influence 24-hr water intake when water was the only available fluid, but did reduce the intake of a preferred solution of saccharin. These findings suggest that activation of brain thyrotropin-releasing hormone systems reduces alcohol intake in primates and that tolerance to this effect is not evident within 5 days under a limited access schedule.

Efficient scheduling of page access in index-based join processing

The paper examines the issue of scheduling page accesses in join processing, and proposes new heuristics for the following scheduling problems: 1) an optimal page access sequence for a join such that there are no page reaccesses using the minimum number of buffer pages, and 2) an optimal page access sequence for a join such that the number of page reaccesses for a given number of buffer pages is minimum. The experimental performance results show that the new heuristics perform better than existing heuristics for the first problem and also perform better for the second problem, provided that the number of available buffer pages is not much less than the optimal buffer size.

Constant absolute ethanol intake by Sardinian alcohol-preferring rats independent of ethanol concentrations.

The present study was designed to evaluate ethanol drinking behaviour in Sardinian alcohol-preferring (sP) and Sardinian alcohol-non-preferring (sNP) rats in the presence of different ethanol concentrations. Ethanol intake was tested under the two-bottle, free-choice regimen and continuous access schedule. Ethanol-naive sP and sNP rats were initially given ethanol solution at the standard, constant concentration of 10% (v/v) for 8 consecutive days (Phase 1). As expected, daily ethanol intake in sP rats rose from 4 to approximately 6 g/kg; in contrast sNP rats consumed < 10 g/kg/day ethanol. Subsequently, an ascending series of ethanol concentrations, ranging from 3 to 60% (v/v), was presented to sP and sNP rats over a 28-day period (Phase 2). At concentrations varying from 7 to 30%, sP rats consumed constant amounts of absolute ethanol per kg of body weight (approximately 6.0 g/kg/day). Daily ethanol intake in sNP rats remained constantly lower than 1.0 g/kg, irrespective of the ethanol concentration. Data from Phase 2 demonstrate the ability of sP rats to precisely adjust daily ethanol intake and support the hypothesis that voluntary ethanol drinking in sP rats is sustained by specific pharmacological effects of ethanol.

Thyrotropin-releasing hormone analog TA-0910 reduces voluntary alcohol intake of P rats subchronically in a limited scheduled access paradigm.

We previously reported that single intraperitoneal injections of the thyrotropin-releasing hormone analog TA-0910 dose-dependently reduce alcohol intake in alcohol-preferring (P) rats in a free-choice continuous access protocol. We later showed, using the same protocol, that a transient tolerance develops to this effect after several consecutive, once-daily injections. In the present study, P rats that had been accustomed to continuous access to alcohol were acclimated to a limited scheduled access protocol in which alcohol was available only between 10 and 11 AM. This resulted in an elevated rate of alcohol intake. Rats were then injected once daily with TA-0910 (0.75 mg/kg) or an equal volume of a saline vehicle at 9:45 AM for 12 consecutive days. After 11 days of scheduled access, rats were allowed continuous access to alcohol. Intake of alcohol and water was measured each day at 11:00 AM. Compared with vehicle, TA-0910 reduced alcohol intake on the 11 days of scheduled access and during the first hour of day 12 when continuous access was restored, but did not reduce total (24 hr) alcohol intake on day 12. Data from this experiment show that TA-0910 reduces alcohol intake over a long period of time in a limited scheduled access protocol.

Apomorphine and 7-OH DPAT reduce ethanol intake of P and HAD rats

Adult male rats of the alcohol-preferring (P) line ( N = 10) and high alcohol drinking (HAD) line ( N = 12) were used to study the effects of IP administration of 0.125–0.50 mg/kg 7-OH DPAT (a putative D 3 agonist) and 0.25–1.0 mg/kg apomorphine (a dopamine agonist with 50-fold higher affinities for the D 1 and D 2 receptors than for the D 3 receptor) on the concurrent intakes of 10% (v/v) ethanol and 0.0125% (g/v) saccharin during a daily 4-h scheduled access period. Control intakes by the P rats for the 4-h period were 17.9±0.5 and 7.2±0.4 ml for the ethanol and saccharin solutions, respectively. For the HAD line, ethanol consumption was 18.7±0.2 ml and saccharin intake was 8.7±1.6 ml for the 4-h period. In terms of grams ethanol/kg body wt., the 4-h intakes were 2.2±0.2 for the P line and 3.0±0.3 for the HAD rats. Both P and HAD rats consumed approximately 40% of their total ethanol intake in the first 15 min of access while consuming only about 15% of their total saccharin intake during this 15-min period. The putative D 3 agonist 7-OH DPAT produced a decrease in ethanol intake in the first h to 45–55% of control levels for the P rat ( p < 0.01) and to 25–70% of control values in the HAD line ( p < 0.001). Apomorphine caused a dose-dependent decrease in ethanol intake in the first hour to 15–70% of control values in the P rat ( p < 0.001) and to 25–60% of control levels in the HAD line ( p < 0.001). Saccharin and 4-h food intakes for both lines were not altered by either 7-OH DPAT or apomorphine. Overall, these results suggest that D 2 and D 3 dopamine receptors may play a role in mediating alcohol drinking behavior of the selectively bred HAD and P lines of rats.

Entrainment and phase shifting of circadian rhythms in mice by forced treadmill running

Daily schedules of spontaneous, drug-, or novelty-induced running can entrain circadian rhythms in rodents. Forced running, by contrast, has been reported to have weak or no effects, although a thorough comparative study in a single species is lacking. To fill this gap, drinking or activity rhythms were monitored in C57 mice subjected to daily, 3-h bouts of forced treadmill running or to 3-h daily access to home cage running wheels. Entrainment to treadmill running was observed in 17/27 mice, and to restricted wheel access in 11/20 mice. Entrainment was affected by availability of a home cage wheel (e.g., 14/16 mice with no wheel entrained to treadmill running). Phase angle of entrainment was related to prior circadian period (τ), and τ following entrainment exhibited aftereffects. No mice entrained to a 3-h daily schedule of water access, suggesting that entrainment to scheduled running was not related to water or associated food intake. Phase shifts in response to single 3-h bouts of treadmill running or wheel access were small and not reliably induced. The entrainment paradigm is thus recommended for further study of behavioral effects on the mouse circadian system; forced running, in particular, offers several methodological advantages. The results do not support prior suggestions that forced and voluntary activity differ in value as nonphotic zeitgebers.

Suppression of alcohol intake after administration of the Chinese herbal medicine, NPI-028, and its derivatives.

The Chinese herbal medicine, NPI-028, has been used for centuries in China to counteract alcohol intoxication. The present study used a number of different experimental conditions to determine whether NPI-028 and its derivatives might selectively influence alcohol intake in rodents that naturally exhibit high alcohol intakes. It was determined that intraperitoneal (i.p.) injections of NPI-028 (0.5, 0.75, and 1.0 g/kg) suppressed alcohol intake by up to 30% in both alcohol-preferring P and Fawn-Hooded (FH) rats during a continuous access schedule. These injections did not significantly affect food or water intakes, nor did the highest dose of NPI-028 (1 g/kg) alter blood ethanol levels after an i.p. injection of 2.5 g/kg of ethanol. In P rats, it was found that NPI-028 was orally active with the dose of 1.5 g/kg having a greater effect on ethanol intake than the 1.0 g/kg dose; once again, food and water intakes were not significantly altered. In FH rats maintained on a limited access schedule (1 hr/day), alcohol intake was completely abolished by 1.5 g/kg of NPI-028. Chronic i.p. administration of NPI-028 (0.75 g/kg) for four consecutive days in FH rats maintained on a continuous access schedule did not lead to any diminution of its alcohol-suppressant effects. Thus, NPI-028 has significant effects on alcohol intake without much effect on water and food intake, and tolerance does not readily develop to these effects. The i.p. administration of a partially purified extract (NPI-031) of NPI-028, obtained by countercurrent chromatography, also dose-dependently suppressed ethanol intake in FH rats, but the highest dose 200 mg/kg) also significantly decreased food intake. Finally, the i.p. administration of puerarin (NPI-31G), an isoflavone isolated from NPI-031 by countercurrent chromatography, significantly reduced ethanol intake in FH rats without affecting food or water intake. Therefore, NPI-028 and one of its pure components, NPI-031G, selectively reduced ethanol intake in alcohol-preferring rats.

Accessing MS-DOS applications over a TCP/IP network

MS-DOS platforms are sometimes used to run specialised applications. An example is an MS-DOS based transputer development system. It is beneficial to have such an application accessible in a networked environment. To be reachable by UNIX machines, TCP/ IP (Internet) protocols must be used. In the article, a software package is described that makes this possible. It consists of a Telnet and a FTP server. Telnet is used to connect to the MS-DOS machine and run applications, while the FTP server is used to transfer files. Various additional functions like user authentication (login) and file access permissions are supported either by the Telnet and FTP servers themselves, or via user login shells. Scheduled access is also possible.

The effects of dopamine agonists on rotational behavior in non-tolerant and caffeine-tolerant rats

Tolerance develops to caffeine-induced stimulation of both locomotor activity and rotational behavior. The role of dopamine in tolerance to the locomotor stimulant effects of caffeine has been documented. However, the role of dopamine in caffeine-induced turning behavior remains to be elucidated. Therefore, the present study determined the role of dopamine receptors in tolerance to caffeine-induced rotational behavior. Rats with a unilateral lesion of the nigrostriatal tract, induced by 6-hydroxydopamine (6-OHDA), were treated chronically with either caffeine (1.0mg/ml) or with drug-free tap water, by a method of scheduled access. Agonists with and without selectivity for dopamine receptor sub-types were tested in both groups of rats (nonselective: apomorphine, d-amphetamine; D1 selective: SKF-38393, SKF-77434; D2 selective: R(-)-propylnorapomorphine (NPA), quinpirole). All drugs produced dose-dependent increases in turning that, with the exception of quinpirole, were comparable in both groups. Quinpirole produced a smaller effect in rats treated with caffeine than in control rats. Thus, there was significant cross-tolerance only to the effects of quinpirole. The concurrent administration of SKF-38393 with NPA produced a synergistic interaction on rotational behavior in control rats, to which cross-tolerance did not develop in caffeine-treated rats. In contrast to what occurs with locomotor activity, in control rats the selective D1 dopamine receptor antagonist SCH 23390 completely blocked SKF-38393-induced turning behavior and the selective D2 dopamine receptor antagonist eticlopride partially attenuated this effect. NPA-induced turning behavior was blocked only by eticlopride; SCH 23390 was without effect. Both SCH 23390 and eticlopride blocked d-amphetamine-induced rotational behavior. The results of this study suggest that D1 dopamine receptors are not involved in tolerance to caffeine-induced rotational behavior. The role of D2 dopamine receptors in this effect is unresolved. Results obtained from rotational behavior studies generally do not parallel those obtained from locomotor activity studies, suggesting that different mechanisms underlie the effects of caffeine on these two behaviors.

Evidence that the amygdala is involved in the inhibitory effects of 5-HT 3 receptor antagonists on alcohol drinking in rats

Two 5-HT 3 receptor antagonists, tropisetron (1 and 10 ng) and ondansetron (10 and 100 ng) were tested for effects on ethanol drinking in Wistar male rats after bilateral microinjection into the amygdala. The animals had limited access (2 h/day) to the 10% (v/v) ethanol solution, food and water were available ad lib during the scheduled access period. Both drugs caused a decrease in ethanol drinking. Tropisetron (1 and 10 ng) decreased ethanol intake during the first hour of access. The lower dose (10 ng) of ondansetron was more effective than the higher (100 ng) dose. The finding implicates amygdaloid 5-HT 3 receptors in the mechanism of ethanol intake in Wistar rats.

The effect of tropisetron injected into the nucleus accumbens septi on ethanol consumption in rats

Earlier studies have shown that 5-HT 3 antagonists possess properties of reducing ethanol (Et0H) preference and intake in EtOH high-preferring rats. In this study we examined the effect of tropisetron (ICS 205–930) microinjection (1 and 10 ng) into the nucleus accumbens septi (NAS) on EtOH drinking in a scheduled access to Et0H paradigm. Control rats received vehicle only. Tropisetron, when injected bilaterally into the NAS, significantly reduced EtOH intake in EtOH high-preferring animals. It is concluded that 5-HT 3 antagonists might exert their antipreference activity by influencing the receptors within the NAS and that 5-HT3 receptors might play an important role in reinforcing properties of EtOH.

Effect of the 5-HT3 antagonist ondansetron on voluntary ethanol intake in rats and mice maintained on a limited access procedure

The effect of the 5-HT3 antagonist ondansetron on ethanol self-administration was examined in a limited access paradigm. Acute administration of ondansetron (0.01 and 0.1 mg/kg) reduced ethanol intake in male Wistar rats by 35%, whilst water intake was unaffected. Both a lower (0.001 mg/kg) and higher dose (1 mg/kg) of ondansetron failed to modify ethanol consumption. Ondansetron did not, however, alter the pharmacokinetic profile of an orally administered dose of ethanol (1 g/kg) over the same dose range. To examine the generality of these findings and to determine if tolerance would develop to the suppressant effects of ondansetron on ethanol intake, male C57BL/6 mice were treated with ondansetron (0.001, 0.01 and 0.1 mg/kg) over 22 days, 30 min prior to scheduled access to ethanol. Both 0.01 and 0.1 mg/kg doses reduced ethanol intake; however, water intake was not altered by either dose. This finding confirms and extends the generality of the effects of 5-HT3 receptor antagonists on ethanol intake across different species and different paradigms of ethanol consumption. More importantly, the present study shows that the reduction in ethanol intake induced by ondansetron was maintained even after a prolonged period of treatment and is not due to an alteration in the absorption or metabolism of ethanol.