Biomedical subjects

J D Sinclair

Publications and source records attributed to J D Sinclair.

105 records · Page 6Linked to original sources

PubMedDate not supplied

Behavioral changes in rats on the day after acute ethanol intoxication.

Activity in computer-monitored running wheels, behavior in open-field tests, body temperature measured by rectal probe, and vocalization were examined in rats after a single injection of 2.5 g/kg ethanol or saline. A reduction in running-wheel activity occurred during intoxication, followed by a significant increase in running 20-24 hr after the injection. Also 24 hr after ethanol, among rats kept in normal cages, there was an increase in body temperature and vocalization and a decrease in ambulation in a dark, quiet open field. Each of these 3 aftereffects was reduced or abolished in the rats with access to a running wheel. The results confirm and extend previous findings of aftereffects of acute intoxication in rats with a time course similar to hangover in humans.

Alcoholic Intoxication↗

PubMedDate not supplied

Brain regional and adrenal monoamine concentrations and behavioral responses to stress in alcohol-preferring AA and alcohol-avoiding ANA rats.

The concentrations of monoamines, precursors and metabolites in various brain regions and the levels of catecholamines in the adrenal glands were determined from naive rats of the AA and ANA lines, and from ones immediately after an escapable shock test. The brain determinations were made with a new step-gradient ion-pair elution method on a reversed phase column and coulometric detection. Several significant differences were observed in the amine concentrations, largely confirming and extending the findings made before the genetic revitalization of the lines: in particular, the AAs, unlike other alcohol-preferring rodents, had higher 5-hydroxytryptamine concentrations. The AA rats tended to have smaller changes than the ANAs in brain aminergic systems and had significantly less change in adrenal epinephrine and dopamine levels after the shock test. The AAs were consistently found to be less active than ANAs in this shock test and in a warm-water swim test, but whether this was a cause or an effect of their brain and adrenal changes could not be determined. Our behavioral results might suggest a reduced reaction of the alcohol-preferring rats to aversive stimulation.

Adrenal Glands↗

PubMedDate not supplied

Lack of alcohol-deprivation effect in AA rats.

Rats that have had at least several weeks of access to ethanol generally react to a week or more without it by drinking more alcohol on the first few days of renewed access. This alcohol-deprivation effect was again seen now in 25 male Long-Evans rats but not in 21 males of the heavy-drinking AA line. The present results obtained with F51 generation AAs differ from ones obtained previously with F32 AAs, which showed an initially small but long-lasting increase after deprivation, and may indicate a change produced by the intervening revitalization of the AA line.

Alcohol Drinking↗

PubMedDate not supplied

Protein, carbohydrate, and ethanol consumption: interactions in AA and ANA rats.

Female rats of the alcohol-preferring AA line were given a choice between protein, carbohydrate, and fat sources. Subsequent free access to alcohol decreased their intake of carbohydrate but not of protein or fat. The individual alcohol intakes were negatively correlated with the carbohydrate intakes (-0.76) and with the alcohol-induced changes in carbohydrate intake (-0.83), but positively correlated with the concurrent protein intakes (0.78). The alcohol consumption and ethanol elimination rate of AA rats were subsequently found to vary directly with the protein content (5, 10, 20 and 40% by energy) of the premixed diet given to them--they drank more than 9 times more ethanol on the 40% than on the 5% protein diet--but the alcohol intake of the alcohol-avoiding ANA rats was not affected by protein intake. The results clearly indicate that the three macronutrients are related to alcohol consumption in different ways, suggesting that protein intake affects the selection of alcohol of AA rats through a factor correlated to ethanol elimination (but not through a ceiling effect from the rate of elimination) and that the alcohol in turn reduces carbohydrate consumption.

Alcohol Drinking↗

PubMedDate not supplied

Demonstration of lever pressing for oral ethanol by rats with no prior training or ethanol experience.

Male rats of the alcohol-preferring AA line were placed in an operant conditioning chamber with one lever delivering 10% alcohol solution and a second giving water. Free food and water were also continually available in the chamber so the animals should not have been motivated to obtain alcohol for reasons of hunger or thirst. The rats had never had alcohol previously. No shaping was used. The rats simply lived for the next 2 weeks in the operant chamber. All of them eventually learned to work for alcohol. Ethanol responding was significantly higher than pressing for water throughout the second week: on the last day, all rats pressed more than 300 times for alcohol and less than 40 times for water, took in a mean of 5.3 +/- 0.2 g/kg of ethanol, and obtained 72% of their total fluid as earned ethanol solution despite the presence of free water. Their acquisition was, however, much slower than that observed in male AA rats that had previously had prolonged access to drinking alcohol in their home cages. Living continually in the operant chamber is thought probably to have been an important factor in enabling the naïve rats to learn to work for alcohol.

Alcohol Drinking↗

PubMedDate not supplied

Long and short alcohol deprivation: effects on AA and P alcohol-preferring rats.

In contrast to all other strains of rats previously tested, the heavy-drinking AA rats were recently found not to increase their daily intake of alcohol after a week without ethanol. This result was now replicated with F52 generation male AAs using Wistars as controls. The same AAs, however, after being switched to a choice between 0.05% saccharin and water, showed a significant increase in saccharin drinking after being deprived of it for a week. Alcohol deprivation for 24 hr or less hardly affected the intake by Wistars during the first hour of renewed intake but sharply increased that by AAs. Still longer deprivation produced progressively smaller first-hour intakes in the AAs. Unlike the AAs, alcohol-preferring P rats showed an increase in alcohol drinking after a week of deprivation similar to that seen with normal rats. However, in common with the AAs, their first hour intake was increased significantly by only a few hours of alcohol deprivation.

Alcohol Drinking↗

PubMedDate not supplied

Initial acceptance of ethanol: gustatory factors and patterns of alcohol drinking.

Individual differences related to taste, determined by prior two-bottle tests of quinine and saccharin selection against water, were found to be related to the initial selection of 15% ethanol solution during the first week of access by 60 randomly bred male rats. The 36 rats that drank the least alcohol during the first week (mean +/- SE: 0.49 +/- 0.06 g/kg/day), however, greatly increased their intake during the second and third weeks, to the level of the 24 initially high alcohol drinkers (4.07 +/- 0.39 g/kg/day during 1st week), and the influence of gustatory factors was no longer apparent. Subsequently, the initially low rats drank less alcohol when saccharin was the alternative fluid. The results can be interpreted as showing that initially low rats, that only drank rather large amounts of alcohol after prolonged exposure, resemble Cloninger's Type 1 alcoholics not only in this temporal pattern but also in being high in novelty seeking, and low in harm avoidance and reward dependence, and that the initially high rats that spontaneously drank rather large amounts even in the first week show the opposite characteristics and resemble Type 2 alcoholics. Although these rats are not themselves models for alcoholism, the results nevertheless suggest it might be possible to develop two separate animal models for the two types of alcoholism.

Alcohol Drinking↗

PubMedDate not supplied

Stimulus-controlled responding for ethanol in AA and Wistar rats.

A method for establishing stimulus control of ethanol responding was developed. After acquisition of lever pressing for oral ethanol, rats of the high-drinking AA (Alko, Alcohol) line and of the moderate-drinking Wistar strain were subjected to alternating 20-min alcohol access periods signaled by a stimulus light, and 40-min nonaccess periods with no light. Ethanol responding during access periods progressively increased and decreased during nonaccess. These changes were faster in the AAs than the Wistars, probably related to differential reinforcement from ethanol. In a second experiment, rats responding under stimulus control were given periods of alcohol deprivation of 3, 6, 12, and 24 h, indicated by a stimulus light. Deprivations shorter than 24 h increased the first-hour intake after renewed access by the AAs, but the Wistars showed no increase until after a 24-h deprivation. The results show stimulus control of ethanol responding and demonstrate the applicability of the procedure for causing ethanol responding to occur at a time chosen by the experimenter.

Alcohol Drinking↗

PubMedDate not supplied

Taste preferences in rat lines selected for low and high alcohol consumption.

Alcohol-avoiding (ANA), alcohol-preferring (AA), and control Wistar rats were tested sequentially for their initial preferences for single concentration solutions of quinine, saccharin, salt, and citric acid, and then for an ascending series of saccharin concentrations. A similar study was subsequently conducted with the alcohol-nonpreferring (NP) and alcohol-preferring (P) rat lines. Both lines developed for low alcohol consumption drank much less saccharin than their respective lines developed for high alcohol intake when tested with the single concentration and with the ascending series. The ANAs also generally drank less of the bitter, salty, and sour solutions than the AAs or Wistars but little difference was found between the NPs and Ps with the other tastes. The curve relating saccharin consumption to concentration reached a maximum at about the same concentrations for AAs, Wistars, NPs, and Ps but for the ANAs, was shifted to the left. The results support a close relationship between the genetic factors influencing alcohol and saccharin intake in both line pairs. This relationship is probably not caused by saccharin tasting like alcohol to a rat, because other results indicate that the NPs do not have more negative reactions initially to the taste of alcohol, but it might be related to similar mechanisms mediating the reinforcement from sweet tastes and from systemic alcohol.

Alcohol Drinking↗

PubMedDate not supplied

The limited access paradigm: description of one method.

Restricting access to alcohol to a short period daily causes rats, in effect, to drink on command. They usually begin drinking alcohol immediately when it is first made available each day and consume a rather constant amount during each access period. The procedure thus has a variety of useful applications. The specific method reported here in detail provides continual access to food and water, but access to unflavored 10% ethanol solution only 1 h/d, all in the home cage, and produces mean alcohol intakes from 0.5-1.0 g/kg in the access hour.

Alcohol Drinking↗

PubMedDate not supplied

Brain ethanol in AA, ANA, and Wistar rats monitored with one-minute microdialysis.

A microdialysis system for measuring the ethanol concentration curve in the nucleus accumbens of the rat brain was developed and tested in three different rat lines (AA, ANA, and Wistar) after an intraperitoneal (IP) and an intragastric (IG) dose of 1.0 g/kg ethanol. The flow rate of the modified Ringer solution was set at 5 microliters/min; samples were taken every minute after ethanol administration and analyzed with headspace gas chromatography. After IP administration, the brain ethanol levels rose much more rapidly than tail blood ethanol levels in the same animals. The maximum brain ethanol level after IG administration was lower and occurred later, and were similar to the tail blood levels in AA and ANA rats. No clear difference between the lines was found after IP administration but there was some indication that ANA rats may absorb alcohol after IG intubation faster than AA or Wistar rats.

Alcohol Drinking↗

PubMedDate not supplied

Dose-related effect of alcohol on mismatch negativity and reaction time performance.

In a recent study, the mismatch negativity (MMN) component of auditory event-related potential, elicited by occasional frequency changes in a repetitive tone, was strongly attenuated by a low dosage of alcohol. We investigated the phenomenon in nine subjects with two different dosages of ethanol (0.35 and 0.55 g/kg), and with two magnitudes of frequency changes (5% and 10%), in a single-blind, placebo-controlled paradigm. Ethanol had no observable effect on the N1 and P2 deflections, nor on the reaction time to frequency changes measured in a separate session. However, the MMN was attenuated after administration of the larger dosage of alcohol, suggesting impaired preconscious processing of stimulus features outside the scope of attention. The results support the view according to which the automatic functions of human information processing are more sensitive than the controlled functions to the detrimental effects of alcohol. The fact that the MMN suppression was stronger when stimulus deviation was smaller indicates that at relatively low blood alcohol concentrations the detection of small deviations is especially hampered.

Acoustic Stimulation↗

PubMedDate not supplied

Evidence about the use of naltrexone and for different ways of using it in the treatment of alcoholism.

Eight double-blind placebo-controlled clinical trials in five countries have demonstrated the safety and efficacy of naltrexone as an adjunct in alcoholism treatment. The efficacy depends, however, on how naltrexone is used. Three of the trials tested naltrexone in two ways: (1) with supportive therapy, i.e. support of complete abstinence; (2) with therapy tacitly accepting that relapses may occur and teaching how to cope with them. Although all found benefits from naltrexone with the coping therapy, none of them found any significant benefit of naltrexone over placebo when combined with support for abstinence. These results are consistent with our pre-clinical studies in which naltrexone, naloxone, and nalmefene were effective when paired with drinking but ineffective when given during abstinence. This supported the hypothesis that the primary mechanism involved is extinction (as had been concluded earlier for the effects of naltrexone in opiate addiction treatment), because extinction only weakens responses that are made while reinforcement is blocked. On this basis, it was proposed that: (1) naltrexone should be administered to patients who were still currently drinking; (2) the instructions should be to take naltrexone only when drinking was anticipated; (3) this treatment should continue indefinitely. Subsequently, clinical trials have found that naltrexone used in this manner is safe and effective.

Alcoholism↗

PubMedDate not supplied

Human cardiorespiratory responses to acute cold exposure.

1. Respiratory and circulatory functions of minimally clad human subjects were studied before and during acute exposure to ambient temperatures of 4.5-6.5 degrees C. 2. After 1 h of cold exposure, subjects showed increases of ventilation, O2 UPTAKE AND CARDIAC OUTPUT. Rectal temperatures fell. 3. During exercise in the cold conditions, oxygen uptake and cardiac output were greater than during the same exercise at normal temperature. 4. The increased cardiac output during cold exposure was achieved by an increase of stroke volume rather than heart rate; this finding is in contrast to changes during bicycle exercise and isometric exercise at normal ambient temperatures. 5. We conclude that the cardiorespiratory effects of cold exposure are not superseded by the response to moderate exercise. The difference between heart rate and stroke volume at increased levels of cardiac output during exercise at normal temperatures and during rest and exercise in cold conditions may be explained by changes of arterial baroreceptor input and of blood catecholamine levels.

Adolescent↗

PubMedDate not supplied

Effects of urethane-chloralose anaesthesia on respiration in the rat.

1. Respiratory effects were measured in rats during six hours' anaesthesia with urethane and chloralose. 2. One-hundred min from urethane administration, minute ventilation (VE) was minimal, arterial PO2 was low, arterial PCO2 was high; tidal volume (VT) and respiratory frequency (f) were relatively constant; hypercarbic and hypoxic responses were substantial. 3. Between 100 and 400 min from urethane administration, minute ventilation and frequency increased and became more variable, tidal volume remained relatively constant, arterial PO2 rose to 100 mmHg, PCO2 fell to 37 mmHg; hypercarbic sensitivity increased and hypoxic sensitivity decreased. 4. We conclude that the anaesthetic regime produced initial depression of respiration relative to metabolism but without great loss of respiratory chemosensitivity. The respiratory depression was prolonged by increased dosage with urethane and chloralose. 5. The variations between hypercarbic and hypoxic responses confirm that they operate through separate mechanisms.

Anesthesia↗