The effect of repeated withdrawal episodes on subsequent withdrawal severity in ethanol-treated rats.

Male rats were given ethanol via an intragastric catheter (8.0-11.0 g/kg per day) for either 8 weeks daily or for four 2-week periods with a 2-week period of no drug treatment intervening between each period of ethanol administration (binge). Older rats were administered ethanol for 2 weeks, to assess the effects of age on ethanol withdrawal as age can alter an animal's sensitivity to ethanol. The presence of physical dependence during withdrawal was assessed on an open field test. Rats that experienced repeated episodes of withdrawal (binge) showed more severe withdrawal signs in successive withdrawal episodes. Older animals showed more severe signs of withdrawal than younger animals after 2 weeks of ethanol treatment. The results of this study lend support to the hypothesis that the experience of withdrawal from ethanol can alter an animal's subsequent response to the drug. Aging appeared to contribute to this effect, but further work is needed to delineate its role.

The effect of repeated withdrawal episodes on acquisition and loss of tolerance to ethanol in ethanol-treated rats.

Male rats were administered ethanol via an intragastric catheter (8.0-12.0 g/kg/day) either continuously for 8 weeks or on a binge schedule with four 2 week cycles of drug administration separated from each successive cycle by a 2 week period of no drug treatment. Older rats were administered ethanol for 2 weeks, to provide an age control for the binge-treated animals as age can alter an animal's sensitivity to ethanol. Acquisition and loss of tolerance to ethanol-induced motor impairment were measured on a dowel task while acquisition and loss of tolerance to ethanol-induced hypothermia were assessed by measuring rectal temperature. Acceleration of tolerance development to both ethanol-induced motor impairment and hypothermia was observed in animals subjected to repeated withdrawal episodes (binge-Study 1) but not in the controls for total dose and duration of drug treatment who experienced withdrawal only once (continuous-Study 2). Persistence of tolerance to ethanol-induced motor impairment occurred in both binge and continuously treated animals while persistence of tolerance to ethanol-induced hypothermia was seen only in the binge treated animals. Age (3 to 7 months) did not affect tolerance development or decay. After three cycles of drug treatment (three withdrawal episodes), binge treated animals showed an impairment in motor ability when blood ethanol levels were near zero. This impairment disappeared when the animals were administered ethanol, indicating a normalizing effect of ethanol on motor behavior in animals subjected to repeated episodes of withdrawal. A similar, but not significant, effect was seen in continuously treated animals. Thus, in an animal exposed to prolonged ethanol treatment, persistent changes in responding to the drug were found. The persistence of these changes was enhanced by the experience of withdrawal from ethanol.

The effect of ethanol and sex on radial arm maze performance in rats.

A daily dose of 1.5 g/kg of ethanol interfered with radial arm maze performance in rats. Ethanol inhibited the acquisition of a new win-shift response to obtain a food reward, especially when a previously learned response was present. This effect was greater in females than in males. Ethanol appears to suppress flexibility in the development of optimal performance of goal-directed behavior.

Effect of electron radiation on aggressive behavior, activity, and hemopoiesis in mice.

The behavioral and physiological effects of 10 Gray (Gy) LINAC electrons in male Swiss-Webster mice were followed for 12 days postirradiation (PR). In Experiment 1, aggressive behavior was assessed in irradiated or sham-irradiated resident mice using a resident-intruder paradigm. Aggressive offensive behavior in the irradiated residents was significantly decreased beginning 2 to 5 days PR, and remained suppressed. Defensive behavior in the nonirradiated intruders was decreased significantly by day 5 PR. In Experiment 2, spontaneous locomotor activity was monitored. Ambulation of irradiated mice was significantly depressed from day 5 PR on, while rearing was affected as early as day 2 PR and remained suppressed. Body weights of irradiated animals were significantly decreased by 5 days PR. In Experiment 3, blood parameters were examined. Compared to sham-irradiated controls, leukocytes, erythrocytes, and hematocrit of irradiated mice were reduced significantly beginning on day 1 PR and remained suppressed, while platelets and hemoglobin were decreased beginning day 2 PR. These results demonstrate that 10 Gy of high-energy electrons results in earlier behavioral deficits than has been observed previously with the same dose of gamma photons.

Repeated withdrawal from ethanol on radial arm acquisition in rats.

Male rats were treated with ethanol (8.0-12.0 g/kg/day) for four 2 week periods interrupted every 2 weeks by a 2 week period of no drug treatment. Thus they experienced withdrawal from ethanol four times. Other rats were treated with ethanol for 8 weeks with no interruptions, to control for the total dose and duration of drug treatment. Acquisition of an eight-arm radial maze response when daily ethanol treatment was ended, was not affected by either the experience of four withdrawals from ethanol or by 8 weeks of ethanol treatment. The lack of withdrawal-induced impairment can be attributed to a lack of sensitivity in the maze task to possible withdrawal-induced deficits and to an insufficient duration of ethanol dependence.

Onset of behavioral effects in mice exposed to 10 Gy 60Co radiation.

The effects of 10 Gray (Gy) 60 Co radiation on social behavior, locomotor activity, and body weight were assessed in individually housed male Swiss-Webster mice. In Experiment 1, aggressive behavior was evaluated prior to irradiation and for 7 d postirradiation by placing an untreated intruder in the irradiated or sham-irradiated resident's home cage for 5 min. Offensive aggressive behavior was not affected significantly by radiation until day 7 postirradiation, when attack latency increased, the frequency and duration of fighting decreased, and the frequency of bites, lunges, and chases decreased. Untreated intruder mice paired with irradiated resident mice showed a decrease in the duration of defensive upright postures and a decrease in the frequency of defensive upright postures, squeaks, and escapes on day 7 postirradiation. In Experiment 2, locomotor activity and body weight were monitored for 7 d postirradiation. Body weight was decreased in irradiated mice beginning 4 d postirradiation. Locomotor activity was suppressed in irradiated animals 90 min after irradiation and remained depressed throughout the 7-d testing period.

Effects of acute sublethal gamma radiation exposure on aggressive behavior in male mice: a dose-response study.

The resident-intruder paradigm was used to assess the effects of gamma radiation (0, 3, 5, 7 Gray [Gy] cobalt-60) on aggressive offensive behavior in resident male mice over a 3-month period. The defensive behavior of nonirradiated intruder mice was also monitored. A dose of 3 Gy had no effect on either the residents' offensive behavior or the defensive behavior of the intruders paired with them. Doses of 5 and 7 Gy produced decreases in offensive behavior of irradiated residents during the second week postirradiation. The nonirradiated intruders paired with these animals displayed decreases in defensive behavior during this time period, indicating a sensitivity to changes in the residents' behavior. After the third week postirradiation, offensive and defensive behavior did not differ significantly between irradiated mice and sham-irradiated controls. This study suggests that sublethal doses of radiation can temporarily suppress aggressive behavior but have no apparent permanent effect on that behavior.

The effect of stress on tolerance to ethanol in rats.

In male rats given 6.0-8.0 g/kg of ethanol/day via gastric intubation, footshock stress accelerated the development of functional tolerance to ethanol (ethanol-induced hypothermia and motor impairment on a dowel task). A primarily psychological stressor (observing other rats that were being shocked) may have retarded tolerance development as subjects in this condition showed no development of functional tolerance. Nonstressed subjects developed tolerance more slowly and required a higher daily dose of ethanol to develop tolerance than shock stressed subjects. Conditioned responses to the drug administration procedure did not appear to play a role in the development of tolerance.