Larry W. Means

Estrogen affects performance of ovariectomized rats in a two-choice water-escape working memory task

To determine if estrogen would protect treated rats from deficits in performance on a working memory task across time, 18 female 6-month-old Sprague-Dawley rats were trained to a criterion on a water-escape spatial delayed matching-to-sample problem. Following training, rats were ovariectomized, and nine were maintained on estrogen (polyestradiol-phosphate, 0.5 mg every 3 weeks) and nine on its vehicle for 200 days. After recovery from surgery, the rats were tested for performance every 6 weeks under three conditions: 5 min retention interval (RI); 30 min RI; and 30 min RI with an emotional experience during the RI. Analysis of correct choices revealed that estrogen-treated rats made more correct choices (p < .05) than controls on the 5 min undisturbed interval; estrogen tended to impair performance on the emotionally distracting interval. Estrogen apparently protected working memory on the undisturbed trials and might be pertinent to the maintenance of memory in female mammals.

Mid-life onset of dietary restriction extends life and prolongs cognitive functioning

Fourteen-month-old C57BL/6 (NIA) mice were placed on a nutritionally complete diet providing 139.4 kcal/week. Over a 2-month period the food ration of experimental mice (AE) was reduced to 85 kcal/week, where it remained for the duration of the study. An aged control group (AC) continued with the higher calorie diet. At age 22 months, AC mice and half of the AE mice (AE22) were given a battery of behavioral tests. The remaining AE mice (AE25) were given the test battery at age 25 months. Also, a middle-aged control group (MC) was tested at age 13 months. Midlife onset caloric restriction (CR) increased longevity and preserved strength, coordination, and spontaneous alternation behavior, and altered responses to enclosed alleys. A spatial discrimination in the Morris water maze and a spatial delayed matching-to-sample water-escape task were insensitive to age and diet. The aged mice were adversely affected by testing.

Prenatal exposure to cocaine II: Effects on open-field activity and cognitive behavior in Sprague-Dawley rats

Pregnant rats received subcutaneous injections of 15 mg/kg of cocaine twice daily (Cocaine-D), twice daily for two consecutive days at 5-day intervals (Cocaine-I), 0.9% saline (Saline) twice daily, or 1.5 mg/kg amfonelic acid (AFA) daily from gestational days 1-20. Offspring were tested for: rates of spontaneous alteration at postnatal days (PND) 32, 35, 40, and 45; acquisition and retention performance on a water maze task beginning at PND 30 and 60; entrance into and activity in an open-field apparatus at PND 60 and 180. The Cocaine-D offspring were less likely than Control offspring to enter the open field when tested at PND 60. The Cocaine-I offspring were hyperactive in the open-field apparatus when tested at PND 60. The drug treated offspring did not differ from the Saline control animals on all other measures. The failure of the Cocaine-D animals to enter the open field is consistent with neophobic behavior that we have observed before in rats exposed in utero to cocaine.

Prenatal exposure to cocaine I: Effects on gestation, development, and activity in Sprague-Dawley rats

Sperm-positive Sprague-Dawley rats received one of four treatments for 20 days beginning within 24 hours of conception. One group received subcutaneous injections of 15 mg/kg cocaine twice daily (Cocaine-D); a second group received 15 mg/kg cocaine twice daily for two consecutive days at 5-day intervals (Cocaine-I); a third group received normal saline twice daily (Saline); and a fourth group received 1.5 mg/kg amfonelic acid (AFA), a dopamine reuptake inhibitor, once daily. Cocaine-D, Cocaine-I, and AFA dams were fed ad lib. An attempt was made to pair-feed the Saline dams with the Cocaine-D dams; however, the Saline dams did not eat as much as the Cocaine-D dams which resulted in dams in all groups essentially eating ad lib. The Cocaine-D pups showed a slightly delayed righting behavior and neophobia at 30 days of age, as evidenced by hypoactivity during the first 15 min of a 6-h activity test. The Cocaine-I pups were hypoactive during the 3-h dark phase of the 6-h activity test when tested at 30 days of age. These effects did not occur in the offspring exposed to AFA, a potent dopamine uptake inhibitor and CNS stimulant which indicate that one or more other sites for cocaine action may combine for its effects on the developing fetus.

Working memory deficits induced by single but not repeated exposures to domoic acid

Single injections of domoic acid, given either intraperitoneally to mice or directly into the hippocampal formation of rats, have been shown to impair learning on the place version of the Morris water maze task and the eight arm radial maze task. The present study was designed to test whether both single and repeated exposures of intraperitoneally administered domoic acid (1.0 or 2.0 mg/kg) impair spatial working memory in mice on a delayed matching-to-sample task. DBA strain mice were given a series of four injections over a 7-day period consisting of either saline or one of two doses of domoic acid. During the 18 days of testing, each subject was given one trial per day consisting of one information run, followed by three test runs. On non-alternation days (days in which the correct response was the same as the preceding day) the saline injected group significantly outperformed the single injection 2.0 mg/kg domoic acid group. This indicates that domoic acid-treated animals were incapable of forming a memory that persisted for 24 h and hence were less able to utilize the prior days experience. However, the repeated exposure groups did not perform as poorly on non-alternation days than the single exposure groups, indicating that domoic acid may affect multiple mechanisms involved in memory consolidation.

Daily glucose injections facilitate performance of a win-stay water-escape working memory task in mice

In an experiment that compared 3 versions of a working memory task, male C57BL/6 mice given either 3 (n = 7) or 5 (n = 7) opportunities (test runs) per trial to choose the escape choice section of a maze acquired a win-stay (spatial matching-to-sample) water-escape task. Mice given only 1 test run per trial (n = 6) were unable to perform above chance level. In a 2nd experiment, 14 mice from the 1st experiment were tested for performance on the 3-test-run version of the task. Each mouse was tested for 12 consecutive days with each of 4 doses of glucose (0, 50, 100, & 250 mg/kg ip) given 30 min before testing. The two higher doses increased the percentage of correct test run choices on all 3 daily test runs across the 12 days of testing. Daily glucose injections facilitated the use of trial-dependent information.

Working memory and the aged rat: Deficient two-choice win-stay water-escape acquisition and retention

Twelve aged (22 months), 12 adult (12 months) and 12 young (3 months) male Fisher 344 rats were compared on acquisition of a two-choice win-stay (spatial delayed matching-to-sample) water-escape working memory task. The 7 aged, 10 adult and 10 young animals that attained criterion were then compared on performance of the task when the retention interval (RI) was 5, 15, 30, 60 and 120 min. They were also compared on retention after being forced to perform an unsolvable water-escape task in a second maze during the first 5 minutes of a 30-minute RI. The aged animals had longer escape latencies, and required more trials and made more errors in attaining a criterion of 9 correct choices over 10 test trials than did the adult and young animals, who did not differ from one another. Also, comparisons of the animals that attained the acquisition criterion revealed that the aged animals had longer escape latencies and made more errors across all RIs and during trials including an interpolated distraction task than did the adult and young animals. The aged animals failed to perform above chance level on tests at any of the RIs or following the distraction task, while the young animals performed above chance level on tests at all intervals and following distraction. The adult animals failed to perform above chance on tests with the 120-minute RI or following distraction. The aged rats were clearly deficient on acquisition and retention of a two-choice water-escape working memory task.

Effects of dorsomedial thalamic lesions on spontaneous alternation, maze, activity and runway performance in the rat.

Abstract A group of 15 Long Evans rats with bilateral electrolytic lesions of the dorsomedial area of the thalamus (DMT) and a group consisting of 14 sham-operated and one normal rat were compared on maze activity, spontaneous alternation, runway acquisition and extinction, and response to a novel alley. The DMT-damaged rats were found to spontaneously alternate at chance level. Also, relative to controls, the experimental animals were slower to habituate locomotion in the maze and more resistant to extinction in the runway. The two groups did not differ significantly on response to novelty.

Comparison of the alcohol-preferring P rat to the Wistar rat in behavioral tests of impulsivity and anxiety.

To determine whether the selectively bred alcohol preferring P rat displays impulsive and anxiety-related behaviors, as have been noted in Type 2 human alcoholics, P rats were compared with outbred Wistar rats, the strain from which P rats were derived, on a series of behaviors reflecting impulsivity and anxiety. The two groups were also compared on their volitional consumption of ethanol. When compared with the Wistar rats, the P rats preferred a higher concentration of ethanol and imbibed a much greater amount of ethanol when they were offered their preferred concentration. However, the behavioral tasks produced inconsistent results. The P rats completed 100 bar presses for food in less time when tested on a constant reinforcement schedule, which suggests that they are hyperactive compared to Wistar rats. However, the P rats also emitted a higher percentage of reinforced responses on differential reinforcement of low rate responding (DRL)-10s and gnawed less from a cork stopper, which suggests that they are less impulsive and possibly neophobic. The two groups did not differ on emergence into or activity in an open field, their activity in or open-arm duration in the elevated plus maze, or performance on DRL-5s and DRL-15s. Collectively, the behavioral data suggest that P rat does not serve as a model for the anxiety and impulsiveness associated with the Type 2 alcoholic individual.

Deficient go, no-go brightness discrimination in rats following hippocampal lesions

Hippocampally ablated, cortically damaged, and intact control rats were trained postoperatively on a discrete-trial, go, no-go brightness discrimination task in an operant situation. The hippocampally ablated animals were found to be deficient on acquisition primarily due to inappropriate responding on no-go (nonieinforced) trials. The deficit is consistent with other operant brightness discrimination studies, but contrasts with the facilitated go, no-go alternation performance exhibited by hippocampally damaged rats.