Behavioral augmentation of tolerance to ethanol in the rat

LeBlanc, A. E.; Gibbins, R. J.; Kalant, H.

doi:10.1007/bf00421426

Cited by 140 publications

(36 citation statements)

References 7 publications

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“…The manner of using the maze was substantially different from that described originally by Chen (1968) and followed by LeBlanc et al (1973). During both training and testing, the room was illuminated only by a 40-W red bulb during training and test sessions.…”

Section: Circular Maze Test Of Learning Impairmentmentioning

confidence: 99%

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Dizocilpine prevents the development of tolerance to ethanol-induced error on a circular maze test

et al. 1996

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Dizocilpine [(+)MK-801] and ketamine, in doses that disrupt learning and memory, also prevent the development of tolerance to the motor impairing effects of ethanol (EtOH). However, dizocilpine itself affects motor behavior. In order to separate the possible influence of these two effects on the development of tolerance to EtOH, food-reinforced performance on a circular maze test was used in two different experiments. EtOH alone (1.2 g/kg) tended to increase the error score and reduce number of runs per trial, running speed, and total distance run, but on chronic administration of EtOH, tolerance developed progressively to all these effects. Dizocilpine also increased the error score, but had a biphasic effect on measures of running: low and intermediate doses (0.009 and 0.075 mg/kg, IP) increased running distance, whereas a high dose (0.15 mg/kg) decreased running speed and distance. When combined with EtOH, dizocilpine tended to overcome the effect of EtOH on running activity, but not on error score. Chronically, dizocilpine (0.075 and 0.15 mg/kg) prevented the development of tolerance to the effect of EtOH on error score, even though the lower dose of dizocilpine permitted tolerance to the effects of EtOH on running. These results suggest that NMDA receptor antagonists selectively inhibit tolerance to cognitive effects of ethanol even when the antagonists do not affect motor performance.

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Section: Circular Maze Test Of Learning Impairmentmentioning

confidence: 99%

“…The animals were run in pairs, following a standard procedure described by LeBlanc et al (1973). Each animal received a 4-min warm-up period which was not scored.…”

Section: Circular Maze Test Of Learning Impairmentmentioning

confidence: 99%

Dizocilpine prevents the development of tolerance to ethanol-induced error on a circular maze test

et al. 1996

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“…It was shown that chronic tolerance to ethanol motor incoordination was facilitated when animals had the opportunity of practicing the task while intoxicated. 37,38 Similarly, Bitrán and Kalant, have shown that learning plays an important role in the development of RT and acute tolerance to ethanol.…”

Section: 3536mentioning

confidence: 97%

Influence of epipregnanolone on the modulation of rapid tolerance to ethanol by neurosteroids

Barbosa

Morato

2007

Rev. Bras. Psiquiatr.

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A b s t r a c t Objective: The objective of the present study was to investigate the effect of epipregnanolone on the influence of neurosteroids on the development of rapid tolerance to the motor impairing and hypothermic effects of ethanol. Method: Experiment 1: on Day 1 groups of mice were pretreated with saline or with epipregnanolone. After 30 min each group was further divided in subgroups that received ethanol or saline. Thirty, 60 and 90 min after the injections the animals were tested on the rota-rod or the body temperature was measured. On Day 2 all groups received ethanol and a similar procedure was followed to evaluate rapid tolerance. Experiment 2 and 3: On Day 1 groups of mice were treated with epipregnanolone and after 15 min each group was divided into three groups in order to receive pregnenolone sulfate, dehydroepiandrosterone sulfate or saline. Thirty minutes later, each group was further divided into two subgroups in order to receive ethanol or saline, respectively, and 30, 60 and 90 min later the animals were tested as in the experiment 1. On Day 2 all groups received ethanol and a similar procedure was followed to evaluate rapid tolerance. Results: Pretreatment with epipregnanolone (0.10-0.30 mg/kg) significantly blocked the development of tolerance to the motor impairing and hypothermic effects induced by ethanol in mice. Considering tolerance to ethanolinduced motor impairment, epipregnanolone (0.15 mg/kg) reversed the stimulatory action of dehydroepiandrosterone sulfate (0.15 mg/kg), but did not affect the actions of pregnenolone sulfate (0.08 mg/kg). Moreover, epipregnanolone prevented the inhibitory action of allotetrahydrodeoxycorticosterone (0.10 mg/kg). In relation to ethanol-induced hypothermia, the results showed that pretreatment with epipregnanolone (0.30 mg/kg) significantly prevented the stimulatory action of dehydroepiandrosterone sulfate and pregnenolone sulfate, as well as the inhibitory action of allotetrahydrodeoxicorticosterone (0.20 mg/kg), on tolerance to this effect. Conclusions: The results suggest a differential interaction between neurosteroids that might modulate the development of rapid tolerance to ethanol.Descriptors: Drug tolerance; Ethanol; Neurologic manifestations; Steroids; Hypothermia Resumo Objetivo: O objetivo do presente estudo foi o de investigar o efeito da epipregnanolona sobre a influência de neuroesteróides no desenvolvimento da tolerância rápida aos efeitos de incoordenação motora e hipotermia induzidos pelo etanol. Método: Experimento 1: no Dia 1, grupos de camundongos foram pré-tratados com salina ou com epipregnanolona. Após 30 min, cada grupo foi subdividido recebendo etanol ou salina. Aos 30, 60 e 90 min após as injeções, os animais foram testados no rota-rod ou a temperatura corporal foi avaliada. No Dia 2, todos os grupos receberam etanol e um procedimento similar foi seguido para avaliar a tolerância rápida. O pré-tratamento com a epipregnanolona (0,10-0,30 mg/kg) bloqueou significantemente o desenvolvimento da tolerância aos efeitos de in...

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“…Por outro lado, não parece provável que o processo de tolerância se deva a eventual redução do acesso da droga ao tecido cerebral, pois tem sido demonstrado, após a administração de uma mesma dose de álcool, iguais concentrações de etanol tanto no cérebro de animais que tiveram aumento de tolerância como naqueles que não tiveram tal aumento 15 In this paper we present the effects of the number of daily toxic doses of alcohol and of the duration of withdrawal period on alcohol tolerance in rats submitted to cycles of 21 doses each. It was observed that alcohol tolerance was increased in animals which received less number of alcohol doses by day and that some degree of tolerance can be detected even after a withdrawal interval of 15 days.…”

Section: Comentáriosmentioning

confidence: 99%

Occurrence of the alcoholic tolerance phenomenon and their relationships with daily frequency of ethanol doses and with the presence of an withdrawal interval, in an experimental model of alcoholism in rats

Cardeal

Cavalheiro

1987

Arq. Neuro-Psiquiatr.

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Sabe-se que o etanol é droga capaz de afetar todas as células do organismo, mas é justamente sobre as do sistema nervoso central que suas influências são mais evidentes, por determinar uma gama de alterações comportamentais. Por muitos séculos tem-se observado que o organismo humano torna-se menos sensível a esses efeitos após o uso da droga, sendo unânime a opinião de que o estudo dessas adaptações pode contribuir para a compreensão do alcoolismo e eventualmente das outras toxicomanias. A maioria dos estudos experimentais sobre a tolerância alcoólica tem sido feita utilizando-se técnicas que permitem obter, em animais, alcoolemias variáveis por determinado período de tempo, após o qual é administrada uma dose padronizada de etanol e observado o desenvolvimento da tolerância aos seus efeitos 3,21,31. Na prática clínica constata-se que alguns indivíduos ingerem diariamente, de modo ininterrupto, quantidades variáveis de alcoólicos como "aperitivos" acompanhando as refeições, enquanto outros ingerem doses por períodos descontínuos de tempo, sendo um ponto comum entre eles, muitas vezes, a tendência para o aumento da quantidade da droga ingerida com o prosseguimento do hábito. O estudo do desenvolvimento do fenômeno de tolerância alcoólica nesses indivíduos, que apresentam distintos comportamentos, poderia contribuir para melhor compreensão do alcoolismo, mas encontram-se limitações práticas, sendo os estudos de tolerância alcoólica feitos quando o hábito está estabelecido e a tolerância alcoólica desenvolvida.Assim sendo, para avaliar eventuais influências do número diário de doses da droga e da presença de um intervalo de abstinência, sobre a tolerância alcoólica, utilizamos modelo experimental de alcoolismo em ratos, desenvolvido pela técnica de entubações gástricas periódicas para a administração do etanol.

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Behavioral augmentation of tolerance to ethanol in the rat

Cited by 140 publications

References 7 publications

Dizocilpine prevents the development of tolerance to ethanol-induced error on a circular maze test

Dizocilpine prevents the development of tolerance to ethanol-induced error on a circular maze test

Influence of epipregnanolone on the modulation of rapid tolerance to ethanol by neurosteroids

Occurrence of the alcoholic tolerance phenomenon and their relationships with daily frequency of ethanol doses and with the presence of an withdrawal interval, in an experimental model of alcoholism in rats

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