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Tolerance to ethanol's effects is seen after chronic injections and after chronic treatment with ethanol-containing liquid diets. However, tolerance associated with injections is often associated with environmental cuing (learned tolerance) and liquid diets do not allow for careful control of dose. The studies reported here demonstrate that chronic (3 g/kg every 6 h for 7 days) intragastric infusion...
The ethanol-induced impairment of rotarod and accelerod performances has been investigated in rats. Ethanol (7.2%, v/v) was given orally ad lib to rats in a modified liquid diet for 15 days. Rotarod and accelerod performances were recorded before and at the 2nd, 4th, 7th, and 15th days of ethanol intake. The daily ethanol consumption of the rats ranged from 12.03 to 16.4 g/kg. Mean blood ethanol...
Motor impairment (tilt-plane) and hypothermia tests were used to further characterize the phenomenon of rapid tolerance to ethanol. Five experiments were carried out to clarify the relationship between rapid and chronic tolerance. The first experiment demonstrated that the extent of tolerance on day 2 produced by the single dose of 4 g/kg alcohol on day 1 was similar to that resulting from two divided...
Chronic nicotine treatment will produce an upregulation of brain nicotinic receptors, and rats treated for 5 months with ethanol had increased [ 3 H]nicotine binding in two of the three brain regions that were studied. However, several studies using short-term treatment did not detect an effect of ethanol on mouse brain nicotinic receptor numbers. Therefore, LS and SS mice were force-fed...
This study was designed to compare the development of tolerance to ethanol in adolescent and adult rats. Rats were pretreated with ethanol (4 g/kg) twice daily by intragastric gavage for 3 or 7 days, and then challenged with a single IP dose of ethanol (5 g/kg). Throughout the pretreatment period body temperature was measured before and after the morning dosage. During the IP challenge test we measured...
Current perspectives on clinical use of N-methyl-d-aspartate (NMDA) receptor antagonists infer acute and repeated administration schedules for management of different pathological states. Development of tolerance and cross-tolerance between different antagonists may significantly affect their clinical effectiveness. Since ethanol was repeatedly demonstrated to act as NMDA receptor antagonist, ethanol...
3,4-Methylenedioxymethamphetamine [(MDMA) or ecstasy] is a popular club drug often used in combination with ethanol. In the current study, we investigated the effects of MDMA and ethanol combinations on locomotor activity and body temperature of rats. For four consecutive days, male Long–Evans rats were treated daily with a 10-mg/kg dose of MDMA with or without a 1.5-g/kg dose of ethanol. 3,4-Methylenedioxymethamphetamine...
Chronic intermittent ethanol exposure (CIEE) in adolescent rats has been shown to produce long-lasting hypnotic, metabolic, and functional tolerance. Recently, it has been hypothesized that allopregnanolone mediates some effects of ethanol, including ethanol-induced impairments in the performance of the Morris Water Maze Task (MWMT). The current studies explore the relationship between cortical and...
Adolescence is a time period when distinct behavioral and neurophysiological changes occur. Novelty seeking is common during this developmental period, and binge alcohol consumption by adolescents is prevalent. Adolescents, as compared to adults, have been shown to display decreased sensitivity to many effects of ethanol, including effects that may serve as cues to moderate consumption. Consequently,...
α-Amino-3-hydroxyl-5-methyl-4-isoxazole-propionate glutamatergic receptors (AMPAR) mediate most of the fast excitatory synaptic transmission in mature neurons. In contrast, a number of developing synapses do not express AMPARs; these are gradually acquired in an activity-driven manner during the first week of life in rats, which is equivalent to the third trimester of human pregnancy. Neuronal stimulation...
During early stages of development rats are highly sensitive to the locomotor stimulating effect of relatively high ethanol doses, an effect strongly modulated by social stress. This ethanol effect can be modulated by pharmacological treatments that also can attenuate the development of ethanol-induced locomotor sensitization in mice. By the end of the preweanling period the mechanisms underlying...
NMDA receptors become a major contributor to acute ethanol intoxication effects at high concentrations as ethanol binds to a unique site on the receptor and inhibits glutamatergic activity in multiple brain areas. Although a convincing body of literature exists on the ability of NMDA receptor antagonists to mimic and worsen cellular and behavioral ethanol effects, receptor agonists have been less...
It has become clear that adolescence is a period of distinct responsiveness to the acute effects of ethanol on learning and other cognitive functions. However, the effects of repeated intermittent ethanol exposure during adolescence on learning and cognition are less well studied, and other effects of repeated ethanol exposure such as withdrawal and chronic tolerance complicate such experiments. Moreover,...
We have previously shown that ethanol-naïve high-alcohol preferring (HAP) mice, genetically predisposed to consume large quantities of alcohol, exhibited heightened sensitivity and more rapid acute functional tolerance (AFT) to alcohol-induced ataxia compared to low-alcohol preferring mice. The goal of the present study was to evaluate the effect of prior alcohol self-administration on these responses...
Understanding how alcohol exposure during adolescence affects aging is a critical but understudied area. In the present study, male rats were exposed to either alcohol or saline during adolescence, then tested every 4 months following either an ethanol or saline challenge; animals were tested until postnatal day (PD) 532. It was found that long-lasting tolerance to high-dose ethanol exists through...
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