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K Gill

Publications and source records attributed to K Gill.

115 records · Page 7Linked to original sources
PubMedDate not supplied

The effects of zimeldine on voluntary ethanol consumption: studies on the mechanism of action.

Research from our laboratory has shown that several specific serotonin uptake blockers (zimeldine, fluoxetine, sertraline) are effective in reducing voluntary ethanol consumption in rats. However, the mechanism of action of these drugs is not well understood. The series of experiments presented here examined whether zimeldine produces its effects on ethanol consumption via a serotonin mediated anorexic action. In addition the effects of chronic administration of zimeldine were examined in rats drinking a dextrose solution, as well as in ethanol-consuming animals following 5-HT depletion with p-chloroamphetamine. The results indicate that zimeldine reduces the consumption of ethanol, dextrose and saccharin solutions. However, these effects on fluid consumption are not blocked by prior serotonin depletion. The results are discussed in terms of serotonin's role in this process in general and the possibility that zimeldine's effects are not directly related to its capacity to block the reuptake of serotonin.

Alcohol Drinking↗
PubMedDate not supplied

Treatment with sertraline, a new serotonin uptake inhibitor, reduces voluntary ethanol consumption in rats.

Serotonin uptake blockers have been shown to produce a robust and reliable reduction in voluntary ethanol consumption in rats. These compounds are currently under investigation as potential treatments for alcohol abuse in humans. It is uncertain whether serotonin uptake blockers exert their effects directly through serotonergic mechanisms or whether an interaction between the serotonin and noradrenergic systems is involved. The present series of experiments was designed to examine the effects of sertraline, a new selective serotonin uptake blocker, on voluntary ethanol intake. Sertraline produced a robust reduction in voluntary ethanol intake. It appears therefore, that increasing selectivity for serotonin blockade does not alter the efficacy of these compounds as antialcohol agents. The drug also reduced the consumption of a saccharin solution indicating that sertraline's effects are not specific to ethanol intake.

1-Naphthylamine↗
PubMedDate not supplied

A further examination of the effects of sertraline on voluntary ethanol consumption.

Previous work with the serotonin uptake blocker, sertraline, demonstrated that the drug suppressed the consumption of ethanol and saccharin as well as body weight gain. There is increasing evidence that many serotonergic agents such as agonists, releasing agents and uptake blockers, reduce food intake. Sertraline was found to have a robust anorexic action. In this paper evidence is presented which supports the hypothesis that the administration of serotonin uptake blockers reduce ethanol consumption as a secondary consequence of a suppression in food intake.

1-Naphthylamine↗
PubMedDate not supplied

Attenuation of voluntary ethanol consumption by dopamine-beta-hydroxylase inhibition (FLA-57): mediated by changes in aversion, reinforcement or both.

The dopamine-beta-hydroxylase inhibitor, FLA-57, was reported by several investigators to reduce voluntary ethanol consumption in rats. The nature of the effect of FLA-57 on this behavior had been attributed to its involvement in both the mediation of positive reinforcing and aversive processes. In the present study, the capacity of FLA-57 to induce a conditioned taste aversion (CTA) in both a forward and a "nominally backward conditioning" paradigms was investigated. This was done in an attempt to assess the possible contribution of a FLA-57-induced CTA to the previously observed reduction in ethanol intake in several drinking studies. Furthermore, the ability of FLA-57 to induce a CTA in a nonnovel situation, where the taste of the presented solution (ethanol or saccharin) was familiar to the animals, was also assessed. The inclusion of these specific conditions was necessitated by the attempt to create conditions similar to those prevalent in drinking studies. We found that FLA-57, in both conditioning paradigms, induced a significant CTA. Animals, naive and experienced with the taste of ethanol or saccharin, exhibited a CTA following the administration of FLA-57. However, the magnitude and rate of extinction of the observed CTAs did not resemble those observed in studies on the effects of FLA-57 on ethanol intake. The results of this study suggest that while it is possible that FLA-57 exerts its effect on ethanol intake, at least in part, through an aversive mechanism, such a mechanism is unlikely to be the exclusive process through which ethanol ingestion is attenuated.

Alcohol Deterrents↗
PubMedDate not supplied

The regulation of alcohol consumption in rats: the role of alcohol-metabolizing enzymes-catalase and aldehyde dehydrogenase.

Aldehyde dehydrogenase (ALDH) and catalase enzymatic activities in brain were assayed and compared to measures of alcohol consumption in two groups of animals screened and maintained on free-choice alcohol access under different conditions. In the first group of Long-Evans rats screened and maintained in home cages, mean alcohol intake was 3.49 g/kg/day with a range of 1.69-5.33 g/kg/day. When alcohol intake (g/kg), total ALDH, low K(m) ALDH, and catalase activities were entered in a multiple regression, a significant correlation of r = 0.51 (p < 0.05) was obtained. In the second group of rats consisting of Long-Evans, P, and NP rats screened using a drinkometer procedure, a multiple correlation between ALDH and catalase enzyme activities and alcohol intake of r = 0.42 (p < 0.05) was obtained. There was a strong relationship between the frequency of alcohol drinking bouts and the activities of catalase and ALDH (r = 0.68, p < 0.0001). The P rats had significantly higher catalase activities than either the NP or Long-Evans rats. The results of the present study confirmed earlier reports on the role of alcohol-metabolizing enzymes in the regulation of alcohol intake. The results also highlighted the fact that the activity of these alcohol-metabolizing enzymes may play a mediating role in patterns of alcohol intake displayed by animals selected for high and low alcohol drinking and also unselected animals.

Alcohol Drinking↗