Developmental alterations of ethanol sensitivity in selectively bred high and low alcohol sensitive rats.

Initial sensitivity and acute tolerance to ethanol have been implicated as risk factors in the development of alcoholism in humans. These behaviors were investigated in rats selectively bred for differences in hypnotic sensitivity following their first dose of ethanol in two different experiments. In Experiment 1, developmental profiles of the association between initial sensitivity and acute tolerance induced by a single exposure to ethanol were examined using male and female high, low, and control alcohol sensitive (HAS, LAS, and CAS) rats. Dose-response curves were constructed for duration of the loss of the righting reflex and for blood ethanol concentration (BEC) at the regain of the righting reflex. Animals were tested with a single ethanol dose ranging from 1.5 to 5.0 g/kg at either 15, 25, 40, 70, 120, or 180 days of age (DOA). For each group, acute tolerance to ethanol was estimated by the slope of the regression line using dose of ethanol and mean BEC at regain. In general, all rat lines showed an increase in hypnotic sensitivity to ethanol with age. To a large degree, the lower sensitivity observed in 15 and 25 DOA HAS and LAS rats was associated with an increase in the development of acute ethanol tolerance relative to older rats. Divergence of the LAS and CAS lines was evident by 25 DOA and remained stable with advancing age. However, HAS rats did not differ significantly from CAS rats until 40 DOA, after which the magnitude of the difference continued to increase with age. In Experiment 2, rats were treated with alcohol at 25, 70, or 180 DOA. Rats at 70 or 180 DOA required less ethanol to disrupt their motor coordination on a rotating dowel (rotarod). Blood ethanol levels were determined at the loss and subsequent regain of the ability to negotiate the rotarod. Total duration of inability to negotiate the rotarod also was recorded. HAS rats were less able to remain on a rotarod while under the influence of alcohol relative to LAS and CAS rats regardless of age. However, no evidence of acute tolerance was observed in this experiment and, in fact, there was evidence of reverse tolerance in that all animals had lower BEC values at regain of ability than they did at loss.

Taste reactivity in high alcohol drinking and low alcohol drinking rats.

High alcohol drinking (HAD) and low alcohol drinking (LAD) rats were tested, in three exposures, for taste reactivity to five concentrations of alcohol (5%, 10%, 20%, 30%, and 40%, v/v), water, and one concentration each of sucrose and quinine. Of the three reactivity exposures, one was done before a 3-week period of continuous access to water and 10% alcohol, the second test was done immediately after the consumption period, and the final reactivity test was done after 1 month of alcohol abstinence. The results showed that the groups did not differ in reactivity on the initial test. After the consumption tests (when the HAD rats consumed significantly more alcohol than the LAD rats), differences in reactivity were found: HAD rats produced significantly more ingestive responses (which promote consumption) and significantly fewer aversive responses (which facilitate fluid rejection) than LAD rats. These differences were maintained even after 1 month of alcohol abstinence. The present data replicate an earlier experiment with alcohol-preferring (P) rats and alcohol-non-preferring (NP) rats, and indicate that the selective breeding process does not produce differences in the innate perception of the taste of alcohol. However, after experience with drinking alcohol, rats selectively bred for high alcohol consumption exhibit a palatability shift reflected by high ingestive responding and little or no aversive responding. Such a shift would clearly contribute to the maintenance of high levels of alcohol consumption.

Alterations in taste reactivity to alcohol in rats given continuous alcohol access followed by abstinence.

Naive, male rats (n = 14) were given continuous access to 10% alcohol and water for a period of 6 weeks. Concurrent taste reactivity tests showed a consistent increase in ingestive responding to a range of alcohol concentrations (10%-40%) over the course of alcohol access. The rats also showed a consistent decrease in aversive responding over time. These data suggested that the palatability of alcohol increased with alcohol experience. After a 1-month period of alcohol abstinence, however, ingestive taste reactivity to alcohol returned to the same level as that found when the rats were alcohol naive, whereas aversive responding approached the level seen initially. A separate control group (n = 13) given only water for the same length of time failed to show similar changes in taste reactivity to alcohol solutions.

Evaluating the palatability of alcohol for rats with measures of taste reactivity, consumption, and lick rate.

In two experiments, rats were presented with water and six concentrations of alcohol (0.5%, 3%, 6%, 9%, 12%, and 15%, v/v) under conditions of mild fluid deprivation. Their responses were measured using taste reactivity (fluids infused directly into the mouth), consumption, and lick rate (both in a voluntary drinking situation). Results in both experiments showed that the number of overall ingestive responses was relatively high and consistent across all alcohol concentrations and water; aversive responding was low for all solutions. During one-bottle, 10-min tests, rats consumed the three lowest concentrations of alcohol (0.5%, 3%, and 6%) and water at an equal level. There was an abrupt drop in the amount of alcohol consumed at 9% and a continued decrease at the two highest concentrations. Lick rates for alcohol (measured only in Experiment 2) fell into three general patterns: 0.5%, 3%, and 6% produced almost identical, negatively accelerating curves consistently above that of water which was linear; lick rates for 9% and 12% rose initially but, at approximately 2 min, became flat; the 15% solution produced a low lick rate throughout the 5-min period. There were significant correlations between lick rate and amount consumed but, contrary to expectations, no significant correlations were found between taste reactivity and the other two measures (consumption and lick rate). These results suggest that taste reactivity to alcohol solutions may be reflective of processes different from those that regulate licking behavior or actual consumption.

Taste reactivity in alcohol preferring and nonpreferring rats.

Taste reactivity tests were used to examine the orofacial responses of alcohol preferring (P) rats and alcohol nonpreferring (NP) rats to the taste of alcohol. In the initial exposure, naive rats were tested for reactivity to five concentrations of alcohol (5%, 10%, 20%, 30%, and 40% v/v), water, and one solution each of sucrose and quinine. A two-bottle consumption test was then given for a 3-week period to allow the rats access to 10% alcohol. After the preference test, a second taste reactivity test was done using the same solutions as in the initial reactivity test. The results indicated no significant differences in taste reactivity between P rats and NP rats on the initial exposure, except that NP rats made significantly more mouth movements. During the two-bottle tests, consumption of alcohol by P rats was consistently higher than that of NP rats across all test days. On the second taste reactivity test, P rats showed an increase in the number of ingestive responses and a decrease in the number of aversive responses to alcohol. NP rats' taste reactivity to alcohol remained unchanged from Exposure 1 to Exposure 2. P rats' and NP rats' responses to sucrose and quinine did not change from Exposure 1 to Exposure 2. It was concluded that there were no innate taste response differences between P and NP rats to alcohol but that following alcohol experience, P rats showed a significant increase in ingestive responses and a concomitant decrease in aversive responses to the taste of alcohol.(ABSTRACT TRUNCATED AT 250 WORDS)

Similarity of taste reactivity responses to alcohol and sucrose mixtures in rats.

The orofacial responses of rats following infusion of taste solutions were examined in two experiments. In the first experiment, naive rats were presented with a 6% alcohol solution and three sucrose mixtures (sucrose combined with quinine hydrochloride, hydrochloric acid, and sodium chloride, respectively) on separate trials and the resulting taste reactivity was examined. The only difference among the solutions was that alcohol elicited a significantly larger number of aversive responses (e.g., gapes, passive drips) than the sucrose mixtures. In the second experiment, naive rats were trained to avoid 6% alcohol using standard conditioned aversion procedures; rats were then tested for reactivity to the three sucrose mixtures and the alcohol solution. With the alcohol solution, trained rats displayed significantly fewer ingestive responses and significantly more aversive responses than control rats. The response of trained rats to the sucrose + quinine solution was similar to that of alcohol: fewer ingestive responses and more aversive responses than control rats. The number of aversive responses to the alcohol and the sucrose + quinine mixture by the trained rats did not differ significantly. Reactivity to the sucrose + hydrochloric acid and sucrose + sodium chloride solutions did not differ between trained rats and control rats. The results suggest that a sucrose + quinine solution has a perceived taste (as revealed by elicited orofacial reflexes) similar to alcohol and that the sucrose mixture is avoided by rats with alcohol aversions because it is unpalatable.