Systemic osmotic manipulations modulate ethanol-induced taurine release : a brain microdialysis study

in Alcohol (2003), 29(1), 11-19

In recent microdialysis studies, increased extracellular concentrations of taurine after high ethanol dose administration were identified in various rat brain regions. The mechanisms by which ethanol ... [more ▼]

In recent microdialysis studies, increased extracellular concentrations of taurine after high ethanol dose administration were identified in various rat brain regions. The mechanisms by which ethanol caused these increases in extracellular taurine concentration remained unclear but could be related to ethanol-induced cell swelling. The aim of the current study was to investigate whether changes in the body osmotic state modulate the effects of ethanol on brain extracellular taurine concentrations. In several groups of rats, brain hypoosmotic or hyperosmotic states were superimposed on acute ethanol (2.0-g/kg) injections, and extracellular taurine concentrations within the nucleus accumbens were assessed by using an intracerebral microdialysis procedure. A hypoosmotic state was obtained by systemic administration of water while hyperosmotic states were induced by intraperitoneal injections of hypertonic saline solutions (1.8% or 3.6% saline). In isoosmotic conditions, ethanol induced an immediate and significant increase in taurine microdialysate content, confirming results of previous studies. However, the effects of ethanol on taurine concentrations were modulated by osmotic manipulations. Hypoosmotic conditions significantly potentiated ethanol-induced taurine release. In contrast, ethanol-induced increases in extracellular taurine levels were attenuated by 1.8% saline injection and totally prevented by 3.6% saline administration. These results strongly argue in favor of a primary role, of osmoregulation in ethanol-induced taurine release. Ethanol-induced cell swelling probably activates volume-sensitive channels, and taurine passively diffuses outside the cells along its concentration gradient. (C) 2003 Elsevier Science Inc. All rights reserved. [less ▲]

Role of acetaldehyde in ethanol-induced conditioned taste aversion in rats

in Psychopharmacology (2003), 167(2), 130-136

Rationale: In spite of many recent studies on the effects of acetaldehyde, it is still unclear whether acetaldehyde mediates the reinforcing and/or aversive effects of ethanol. Objectives: The present ... [more ▼]

Rationale: In spite of many recent studies on the effects of acetaldehyde, it is still unclear whether acetaldehyde mediates the reinforcing and/or aversive effects of ethanol. Objectives: The present study reexamined the role of acetaldehyde in ethanol-induced conditioned taste aversion (CTA). A first experiment compared ethanol- and acetaldehyde-induced CTA. In a second experiment, cyanamide, an aldehyde dehydrogenase inhibitor, was administered before conditioning with either ethanol or acetaldehyde to investigate the effects of acetaldehyde accumulation. Methods: A classic CTA protocol was used to associate the taste of a saccharin solution with either ethanol or acetaldehyde injections. In experiment 1, saccharin consumption was followed by injections of either ethanol (0, 0.5, 1.0, 1.5 or 2.0 g/kg) or acetaldehyde (0, 100, 170 or 300 mg/kg). In experiment 2, the rats were pretreated with either saline or cyanamide (25 mg/kg) before conditioning with either ethanol or acetaldehyde. Results: Both ethanol and acetaldehyde induced significant CTA. However, ethanol produced a very strong CTA relative to acetaldehyde that induced only a weak CTA even at toxic doses. Cyanamide pretreatments significantly potentiated ethanol- but not acetaldehyde-induced CTA. Conclusions: The present results indicate that ethanol-induced CTA does not result from brain acetaldehyde effects. In contrast, it is suggested that the reinforcing effects of brain acetaldehyde might actually reduce ethanol-induced CTA. Our results also suggest that the inhibition of brain catalase activity may contribute to the potentiating effects of cyanamide on ethanol-induced CTA. [less ▲]

Acamprosate reduces context-dependent ethanol effects

in Psychopharmacology (2002), 164(1), 10-18

Rationale: Previous studies have indicated that the conditioned effects of environmental stimuli contribute to ethanol tolerance and abuse. Acamprosate was recently suggested to reduce the effects of ... [more ▼]

Rationale: Previous studies have indicated that the conditioned effects of environmental stimuli contribute to ethanol tolerance and abuse. Acamprosate was recently suggested to reduce the effects of environmental stimuli previously associated with ethanol administrations. This action is believed to contribute to the clinical benefits of acamprosate treatment in alcoholics. Objectives: In the present experiment, a classical drug-conditioning paradigm was used to test whether acamprosate modulates the effects of ethanol-paired environmental stimuli on spontaneous motor activity. Methods: Wistar rats were divided into three groups: cued, uncued and control. The cued group daily received ethanol injections (2.0 g/kg, IP) in a specific testing environment. The uncued group daily received ethanol injections (2.0 g/kg, IP) in their home cage but never experienced ethanol in the testing environment. The control group was injected with saline and never experienced ethanol. After 8 conditioning days, the rats were IP injected with various ethanol doses (saline, 1.0, 1.5 or 2.0 g/kg) and their spontaneous motor activity in the testing environment was recorded to investigate their respective tolerance to ethanol inhibitory effects. In the second part of the study, the same procedure was repeated with chronically acamprosate-treated rats. The chronic acamprosate treatment (400 mg/kg per day) started 2 weeks before the conditioning procedure by diluting acamprosate in the drinking bottles and was maintained throughout the whole experiment. Results: The cued rats showed a significant environment-dependent tolerance to ethanol inhibitory effects relative to the uncued and control rats. This higher ethanol tolerance of the cued rats was mainly due to a faster recovery from ethanol's inhibitory effects on spontaneous activity. Furthermore, the cued rats showed a higher level of activity in the testing environment after the saline injection. However, it is not clear whether this hyperactivity is a conditioned compensatory response or an increased exploratory behavior. Acamprosate totally abolished the environment-dependent tolerance to ethanol, whereas it did not alter the hyperactivity of the cued rats in the testing environment. Conclusions: The results of the present study suggest that acamprosate reduces ethanol-conditioned effects. Such an action may be of importance to explain the anti-relapse effects of acamprosate. [less ▲]

Conditioned stimulus preference after acetaldehyde but not ethanol injections

in Pharmacology, Biochemistry & Behavior (2001), 68

Acetaldehyde, the first ethanol metabolite, has been suggested to mediate some of the behavioral effects of ethanol and particularly its reinforcing properties, although this later hypothesis remains ... [more ▼]

Acetaldehyde, the first ethanol metabolite, has been suggested to mediate some of the behavioral effects of ethanol and particularly its reinforcing properties, although this later hypothesis remains extremely controversial. While several studies demonstrated the reinforcing effects of brain acetaldehyde, blood acetaldehyde accumulation is believed to be primarily aversive. In the present study, a conditioned reinforcement procedure has been used to investigate the reinforcing and/or aversive effects of intraperitoneal injections of both acetaldehyde and ethanol in Wistar rats. An olfactory stimulus was paired with daily injections of either ethanol (0, 0.25, 0.5, 1 and 2 g/kg) or acetaldehyde (0, 10, 20, 100 and 150 mg/kg). After eight conditioning sessions, all rats were tested for their stimulus preference or aversion. The results show that conditioning with small, 0.25 and 0.5 g/kg, ethanol doses induced neither preference nor aversion for the olfactory cue. In contrast, higher ethanol doses (1.0 and 2.0 g/kg) resulted in significant stimulus aversions. Acetaldehyde conditioning led to a biphasic stimulus preference, with a maximal preference around 20 mg/kg acetaldehyde. No evidence of aversive effects was found with increasing doses of acetaldehyde, even with concentrations close to the lethal limit. The present study clearly shows that systemic acetaldehyde injections induced significant stimulus preferences. This suggests that acetaldehyde may be, at least in part, responsible for the reinforcing effects of alcohol intake. [less ▲]

Implications of acetaldehyde in ethanol reinforcing and discriminative effects

in Alcohol & Alcoholism (2001), 36

Neurochemical and behavioral effects of ethnaol-conditioned stimuli: implication for alcohol consumption

in Cahiers de l'I.R.E.B. (2001), 15

Taurine and ethanol preference : a microdialysis study using Sardinian alcohol-preferring and non-preferring rats

in European Neuropsychopharmacology (2000), 10

Recent intracerebral microdialysis studies of different rat brain regions have shown that an acute ethanol injection induced a rapid dose-dependent increase in taurine microdialysate content during the ... [more ▼]

Recent intracerebral microdialysis studies of different rat brain regions have shown that an acute ethanol injection induced a rapid dose-dependent increase in taurine microdialysate content during the first 60-min period. In taurine-supplemented rats, a reduced aversion for high ethanol doses was observed in a place conditioning paradigm, suggesting that taurine may be implicated in the regulation of some adverse effects of ethanol. The present study compares the effects of acute ethanol injections (1.0 and 2.0 g/ kg, i.p.) on taurine nucleus accumbens microdialysate content in Sardinian ethanol-preferring (sP) and Sardinian ethanol-non preferring (sNP) rats. While neither saline nor 1.0 g/kg ethanol injections had significant effect on taurine microdialysate concentration, 2.0 g/kg ethanol administration induced a rapid and significant increase in taurine microdialysate content in both sP and sNP rats. However, this ethanol-induced taurine release was significantly reduced in sP rats by comparison to sNP rats. As taurine is suggested to be released by brain cells to modulate different ethanol adverse effects, this lower taurine responsiveness to ethanol in sP rats by comparison to both sNP and Wistar rats may be a relevant indicator of reduced ethanol aversive effects in such animals and therefore be related to their higher alcohol consumption. [less ▲]

Ethanol induces taurine release in the amygdala: an in vivo microdialysis study

in Addiction Biology (1999), 4

The effect of acute IP ethanol injections on the extracellular aspartate, glutamate, taurine and GABA content of the basolateral amygdala microdialysate was investigated in relationship with the total ... [more ▼]

The effect of acute IP ethanol injections on the extracellular aspartate, glutamate, taurine and GABA content of the basolateral amygdala microdialysate was investigated in relationship with the total brain ethanol content. Each acute intraperitoneal injection of ethanol, 0.5, 1.0, 2.0 and 3.0 g/kg body weight, induced an immediate increase in the microdialysate taurine content; both 0.5 and 1.0 g/kg ethanol evoked an increase during the first 20 minutes following injection which returned to baseline value by 40 minutes despite the fact that ethanol was detectable in the brain until 60 or 120 minutes respectively; after either 2.0 or 3.0 g/kg ethanol there was an increase in taurine content of gradual intensity which gradually declined to reach baseline values by 100 minutes. In contrast, the ethanol concentration for 2.0 g/kg remained elevated at the end of the 120 minutes approximately 25 mg ethanol / mg protein. The stimulated release of taurine within the amygdala could participate in the regulation of the ethanol-induced changes in osmolarity, since taurine is postulated to act as an osmoregulator in the brain. Taurine could also mediate or interact with the ethanol-induced CNS effects, as it exerts a modulatory action on cell excitability and neurotransmitter processes. [less ▲]

Changes in the amygdala amino acid microdialysate after conditioning with a cue associated with ethanol

in Alcohol & Alcoholism (1999), 34

The excitatory amino acid neurotransmission within the amygdala has been implicated in learning associations between external stimuli and intrinsic reward values such that it may play a key role in ... [more ▼]

The excitatory amino acid neurotransmission within the amygdala has been implicated in learning associations between external stimuli and intrinsic reward values such that it may play a key role in conditioned drug effects. In the present studies, the responses of the excitatory amino acids, aspartate and glutamate together with the neuromodulatory sulphonated amino acid taurine, within the basolateral amygdala, to an odor cue repeatedly associated with acute ethanol injections (2g/kg, IP) have been investigated by a microdialysis technique combined with HPLC-EC analysis. After presentation of the ethanol-conditioned stimulus, a single IP saline injection induced an immediate and significant increase in the taurine microdialysate content which could be related to the neuromodulatory action of taurine. Furthermore, when the conditioned stimulus was combined with the ethanol injection (2g/kg, IP), significant increases in both taurine and glutamate microdialysate content were observed and indicated a learned compensatory response to counteract the acute effects of ethanol. These results demonstrate that changes in amygdala extracellular glutamate and taurine concentrations can be conditioned to ethanol-associated stimuli and are therefore probably implicated in the phenomenon of environmental-dependent tolerance to ethanol. [less ▲]

Changes in the amygdala amino acid microdialysate after conditioning with a cue associated with ethanol

in Psychopharmacology (1998), 139

Excitatory amino acid neurotransmission within the amygdala has been implicated in learning associations between external stimuli and intrinsic reward values, such that it may play a key role in ... [more ▼]

Excitatory amino acid neurotransmission within the amygdala has been implicated in learning associations between external stimuli and intrinsic reward values, such that it may play a key role in conditioned drug effects. In the present studies, the responses of the excitatory amino acids, aspartate and glutamate, together with the neuromodulatory sulphonated amino acid, taurine, within the basolateral amygdala, to an odor cue repeatedly associated with acute ethanol injections (2 g/kg, IP) have been investigated by a microdialysis technique combined with HPLC-EC analysis. After presentation of the ethanol-conditioned stimulus, a single IP saline injection induced an immediate and significant increase in the taurine microdialysate content which could be related to the neuromodulatory action of taurine. Furthermore, when the conditioned stimulus was combined with the ethanol injection (2 g/kg, IP), significant increases in both taurine and glutamate microdialysate content were observed and indicated a learned compensatory response to counteract the acute effects of ethanol. These results demonstrate that changes in amygdala extracellular glutamate and taurine concentrations can be conditioned to ethanol-associated stimuli and are therefore probably implicated in the phenomenon of environmental-dependent tolerance to ethanol. [less ▲]