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Biomedical subjects

J D Sinclair

Publications and source records attributed to J D Sinclair.

At least 19 recordsLinked to original sources
PubMed1992

Localization of the primary sites of genetic influence.

When studying the nervous system of animal lines developed for specific genetically-determined behavioral differences, how does one tell whether a difference between the lines found at one specific location was caused by a direct genetic interaction at that location or by an interaction at some distant site which was then imposed on the tested location? The form of the line difference can help to answer this question. One particular form, called an inverse line difference, is shown to have a higher probability of being close to the location of the direct gentic interaction.

Alcohol Drinking↗
PubMed1992

Alcohol elimination and the regulation of alcohol consumption in AA and ANA rats.

Previous studies have usually found that animals with either higher alcohol elimination rates or ADH (alcohol dehydrogenase, EC1.I.I.I) activities have higher voluntary intakes of alcohol than ones with lower elimination rates. This relationship has now been studied in the AA and ANA rat lines genetically developed, respectively, for high and low alcohol consumption. Female AA and ANA rats had their alcohol elimination rate measured before being given a free choice between 10% (v/v) alcohol and water for 3 weeks. The elimination rate was then measured again and liver ADH activity was determined. The alcohol elimination rate was significantly higher in AA than ANA rats before drinking and was increased by alcohol drinking in AA but not ANA rats. ADH activity was similar in both lines and unrelated to either alcohol drinking or elimination rates, suggesting that the enzyme activity is not a rate-limiting factor in the alcohol metabolism of these two lines. The present results support the conclusion that alcohol elimination and alcohol consumption are partially determined by genetics. Furthermore, although alcohol elimination itself probably does not have direct control over drinking, some factor related to the alcohol elimination rate appears to be among the mechanisms influencing the level of alcohol drinking.

Alcohol Dehydrogenase↗
PubMed1991

Respiratory patterns in anesthetised rats before and after anemic decerebration.

Experiments were undertaken to test the comparability of changes in respiratory frequency and tidal volume during hypoxia and hypercapnia in rats with and without intact peripheral chemoreceptors and with intact vagi. Neural organisation of respiratory control was perturbed by anemic decerebration, achieved by ligation of the common carotid and basilar arteries. Ischemia of the brain was produced as far candal as the rostral pontine nuclei involved in respiratory control but left the medulla well perfused. The dominant respiratory effect in animals breathing air or oxygen was polypnea with hypocapnia (mean PaCO2 when breathing air 24.7 mmHg, when breathing oxygen 29.6 mmHg). After decerebration the increase of ventilation produced by breathing 10% O2 in N2 was reduced compared with responses in the intact state but levels of ventilation (V1) in hypoxia were similar to those before decerebration. After decerebration, the increase of ventilation produced by breathing 5% CO2 was greatly reduced and the level of V1 in animals breathing CO2 was significantly less than in the intact state. Intermediate changes were seen in animals breathing 2-3% CO2 which converted the hypocapnia (PaCO2 30.9 mmHg) to eucapnia (PaCO2 46.4 mmHg). In the intact state, hypoxia dominantly caused increased frequency (f) and hypercapnia caused increased tidal volume (VT); after decerebration, hypoxia produced reduction of VT while hypercapnia produced reduction of f. Bilateral carotid sinus nerve section in decerebrate animals eliminated the ventilatory response to hypoxia but left the responses to hypercapnia unaltered. The results point to differences in the mechanisms by which hypoxia and hypercapnia influence respiration in both intact and decerebrate animals with carotid sinus and vagus nerves functional. The differences can now be interpreted in terms of specific neural features of respiratory control.

Anemia↗
PubMed1991

Effects of hypoxia and cold acclimation on thermoregulation in the rat.

The effects of hypoxia (inspired O2 fraction = 0.12) on thermoregulation and on the different sources of thermogenesis were studied in rats before and after periods of 1-4 wk of cold acclimation. Measurements of metabolic rate (VO2) and body temperature (Tb) were made at 5-min intervals, and shivering activity was recorded continuously in groups of rats subjected to three protocols. In protocol 1, rats were exposed to normoxia to an ambient temperature (Ta) of 5 degrees C for 2 h. In protocol 2, at Ta of 5 degrees C, rats were exposed for 30 min to normoxia, then for 45 min to hypoxia, and finally for 30 min to normoxia. In protocol 3, in the non-cold-acclimated (NCA) rats, Ta was decreased from 30 to 5 degrees C in steps of 5 degrees C and of 30-min duration while in cold-acclimated (CA) rats at 5 degrees C for 4-wk, Ta was increased from 5 to 30 degrees C in steps of 5 degrees C and of 30-min duration. Recordings were made in normoxia and in hypoxia on different days in the same animals. The results showed that 1) in NCA rats, cold exposure in normoxia induced increases in VO2 and shivering that were proportional to the decrease in Ta; 2) in CA rats in normoxia, for a given Ta, VO2 and Tb were higher than in NCA rats, whereas shivering was generally lower; and 3) in both NCA and CA rats, hypoxia induced a transient decrease in shivering and a sustained decrease in nonshivering thermogenesis associated with a marked decrease in Tb that was about the same in NCA and CA rats. We speculate that hypoxia acts on Tb control to produce a general inhibition of thermogenesis. Nonshivering thermogenesis is markedly sensitive to hypoxia, especially demonstrable in CA rats; a recovery or even an increase in shivering can compensate for the decrease in nonshivering thermogenesis.

Acclimatization↗
PubMed1991

Determinants of alcohol preference in the AA and ANA rat lines selected for differential ethanol intake.

A selective breeding program conducted in this laboratory has resulted in the establishment of the alcohol-preferring AA (Alko Alcohol) and alcohol-avoiding ANA (Alko Nonalcohol) rat lines. These lines have been used as a tool for attempting to identify the behavioral, neurochemical, and biochemical correlates of differential voluntary ethanol consumption. Some of the differences that have been found between the lines involve differential reinforcement: AA rats, but not ANA rats, rapidly acquire an ethanol-reinforced operant response. The AA's greater development of tolerance to the depressant effects of ethanol and their faster ethanol metabolism would also allow them to drink more. Neurochemical studies have suggested differential functioning of brain monoaminergic mechanisms. The activity of tyrosine hydroxylase and dopa decarboxylase, and the brain dopamine concentrations are higher in the AA rats than in the ANA rats, and the maximal number of dopamine D2 receptors is lower in the AA rats. The concentration of noradrenaline is higher in the brain of ANA rats than in that of AA rats, while the 5-hydroxytryptamine levels do not seem to differ greatly. The importance of these differences to the line difference in ethanol intake is not, however, clear, since there appears to be no difference in the sensitivity of monoamine systems of the two lines to ethanol.

Alcohol Drinking↗
PubMed1979

Alcohol-deprivation effect in rats genetically selected for their ethanol preference.

Alcohol deprivation and alternate-day access increase voluntary alcohol drinking by normal rat strains in a consistent manner. In contrast, the ANA strain developed by selective outbreeding for low alcohol intake during continuous access showed no increase in their alcohol drinking during alternate-day access and only a small increase after a week of deprivation. The AA strain developed for high alcohol intake showed an increase after a week of deprivation similar in magnitude to that of normal rats but persisting much longer. In order to have been selected, these deviant reactions to deprivation must have been related to deviant baseline levels of alcohol drinking during continuous access, but presently even the AAs with the lowest baselines show the persistent increase and the ANAs with the highest baselines show only small increases. Strain differences were also found in spontaneous alternation in a T-maze. A modification of Pinel and Huang's inhibitory factor model accounting for these results is presented.

Alcohol Drinking↗
PubMed1978

Passing remarks.

Explore the source record for details and available documents.

Cardiac Catheterization↗
PubMed1976

Thoracic and arterial pressures, blood flow and syncope.

The relationship between elevation of the thoracic pressure and the thoracic volume and blood pressure was investigated in man. Raising the thoracic pressure produced an increasing hypotension and ultimately fainting. Cine-radiography showed a reduction in heart size while the high thoracic pressure was maintained.

Animals↗
PubMed1976

Motivation for alcohol in rats: position and bottle preferences do not cause drinking.

Position preference, i.e., the tendency to drink from onelocation rather than the other, was found to be relatively unimportant in determining the drinking behavior of rats presented with a choice between water and a 7% (v/v) ethanol solution in typical two-bottle choice situations. It accounted for essentially none of the variance in rats generally drinking more alcohol solution than water after prolonged previous alcohol experience, and in rats consuming very little alcohol; only in rats drinking slightly less alcohol solution than water was it found to have an influence. Similarly, bottle preference, i.e., the tendency to drink from one of the two bottles regardless of its position or contents, andposition preference were found to have almost no effect on heavy-drinking rats even on their first day of exposure and on low-drinking rats after about three days of access to alcohol.

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↗