Ethanol-induced hypothermia in rats is antagonized by dexamethasone

The effect of dexamethasone on ethanol-induced hypothermia was investigated in 3.5-month old male Wistar rats (N = 10 animals per group). The animals were pretreated with dexamethasone (2.0 mg/kg, ip; volume of injection = 1 ml/kg) 15 min before ethanol administration (2.0, 3.0 and 4.0 g/kg, ip; 20 per cent w/v) and the colon temperature was monitored with a digital thermometer 30, 60 and 90 min after ethanol administration. Ethanol treatment produced dose-dependent hypothermia throughout the experiment (-1.84 ñ 0.10, -2.79 ñ 0.09 and -3.79 ñ 0.l5 degrees Celsius for 2.0, 3.0 and 4.0 g/kg ethanol, respectively, 30 min after ethanol) but only the effects of 2.0 and 3.0 g/kg ethanol were significantly antagonized (-0.57 ñ 0.09 and - 1.25 ñ 0.10, respectively, 30 min after ethanol) by pretreatment with dexamethasone (ANOVA, P<0.05). These results are in agreement with data from the literature on the rapid antagonism by glucocorticoids of other effects of ethanol. The antagonism was obtained after a short period of time, suggesting that the effect of dexamethasone is different from the classical actions of corticosteroids.

N-methyl-D-aspartate receptors, nitric oxide, and ethanol tolerance

Several experimental models have been used to study tolerance to ethanol. The development of tolerance to the motor incoordinating effect of a single administration of ethanol occurs within 8-24 h after the effect of the first dose has disappeared. This form of tolerance is designated rapid tolerance and seems to involve functional rather than pharmacokinetic mechanisms. Like chronic tolerance, rapid tolerance has been shown to be infiuenced by processes related to learning and memory. It is known that N-methyl-D-aspartate (NMDA) receptor systems are involved in the expression and maintenance of one form of long-term potentiation (LTP), a synaptic adaptive process which has been suggested to be the cellular basis of memory or associative memory. Considering the similarities between learning and tolerance, the effects of NMDA agonists and antagonists on tolerance to ethanol were investigated. Our studies demonstrated that NMDA antagonists that impair learning, such as dizocilpine or ketamine, inhibit tolerance, while NMDA agonists that improve learning, such as D-cycloserine, increase tolerance. Moreover, the nitric oxide synthase inhibitor L-nitroarginine blocks tolerance to the effects of ethanol. Taken together, these data confirm the involvement of the NMDA system in ethanol tolerance and emphasize the participation of leaming in this phenomenon.

The development of tolerance to ataxia and to diuresis induced by ethanol in rats is not simultaneous

The present study was conducted to determine whether behaviorally accelerated development of tolerance to the disruptive effects of ethanol on rotarod performance paralleled the development of tolerance to ethanol-induced diuresis and to determine the effect of pre-and post-training ethanol administration on the development of tolerance to both of these effects. Male Wistar rats were treated with ethanol (2gKg-1 day-1, ip) over a preiod of 5 weeks under one of the following schemes: ethanol injections before training (pre-training ethanolgroup) or after training (post-training ethanol group). Control animals received 0.9% NaCl, ip, after training. The effect of ethanol on diuresis was assessed once a week. Data are reported as means ñ SEM of 6 animals. Significant tolerance to the uncoordinating effect of ethanol was detected from the 17th day of treatment onwards in animals of the pre-training group (2nd day = 1.7 ñ 0.6s vs 17th day = 39.0 ñ 8.1s, Student t-test for related samples)but was not observed in animnals of the post-training ethanol group until 34 day of treatment (pre-training ethanol group = 56.1 ñ 8.5s; post-training ethanol group= 29.8 ñ 9.6s vs control group = 12.6 ñ 7.6s, Newman-Kleuls test). In contrast, the development of tolerance to the diuretic effect of ethanol was similar in both groups and appeared after 4 weeks of treatment (pre-training ethanol group: 28th day = 1.9 ñ 0.7 ml vs lst day = 4.0 ñ 0.5ml, Student t-test for related samples; post-training ethanol group: 28th day = 1.0 ñ ml vs 1st day = 3.1 ñ 0.30.6ml vs 1st day = 3.1 ñ 0.3ml, Student t-test for related samples). These data suggest that tolerance to the motor incapacitating effect of ethanol does not affect the time course of tolerance of ethanol-induced diuresis and thus, the two processes involve independent mechanisms. Moreover, the data confirm that tolerance to the disruptive effect of ethanol on rotarod performance can be influenced by the scheme f training

Indomethacin affects the development of tolerance to ethanol-induced diuresis

The present study analyzes the effects of indomethacin on the development of tolerance to the diuretic effect of ethanol. Male Wistar rats were with ethanol (2gKg-1 day-1) over a period of 4 weeks and the effect of ethanol on diuresis was assessed weekly. A significant tolerance to the diuretic effect of ethanol was detected after 3 weeks of treatment. However, rats treatment simultaneously with ethanol plus indomethacin (5mg/Kg, ip,, on alternate days) showed no tolerance to ethanol even after 4 weeks of treatment. The fact that indonethacin prevented the development of tolerance to the diuretic effect of ethanol but no influence on diuresis per se suggests that prostaglandins play a significant role in the mechanisms of tolerance to ethanol

Behavioral and biochemical changes following reapeted administration of carbaryl to aging rats

Motor, sensory and thermoregulatoty function were examined in aging rats (12 months) following two schedules of repated po adminstration of the carbamate insecticide carbaryl and these effects were assessed in terms of blood cholinesterase activity. Administration of carbaryl (50 mg/Kg) by gavage daily for 30 days resulted in a resultad in a reduction of locomotor activity in thre open-field and an inhibition of cholinesterase activity within 30 min after the last treatment. Twenty-for h later, only the locomotor effect was evident. After 90 days of exposure to carbaryl in drinking water, no significant effects were observed. These findings suggest that repeated administration of carbaril to aging rats can induce an impairment of motor function and a reduction of cholinesterase activity, while tolerance develops in some other parameters