Behavioral and neurochemical effects induced by alcohol-conditioned stimuli

in Cahiers de l'I.R.E.B. (2000), 14

Bases neurobiologiques des comportements d’alcoolisation: implication des acides aminés neuro-excitateurs et neuro-inhibiteurs

Doctoral thesis (1999)

Les théories traditionnelles qui essaient d’expliquer le phénomène d’addiction rencontrent généralement de grandes difficultés à rendre compte de deux particularités importantes de cet état de ... [more ▼]

Les théories traditionnelles qui essaient d’expliquer le phénomène d’addiction rencontrent généralement de grandes difficultés à rendre compte de deux particularités importantes de cet état de pharmacodépendance: le caractère compulsif de la consommation de drogue et la très grande fréquence des rechutes parfois très longtemps après le sevrage. Les théories de l’apprentissage par conditionnement apportent une solution originale à ces questions non résolues. En effet, de nombreuses expériences animales ont démontré que des stimuli environnementaux associés de manière répétée à l’administration de ces drogues peuvent acquérir le statut de stimuli conditionnés capables d’induire à eux seuls certains effets physiologiques et comportementaux spécifiques. On a de plus suggéré que ces réponses conditionnées sont responsables du déclenchement des comportements compulsifs de recherche de drogue et participent dès lors aux rechutes dans sa consommation incontrôlée. Parmi les drogues addictives, l’alcool est probablement la substance la plus difficile à étudier. En effet, sa simplicité moléculaire lui permet paradoxalement d’affecter tous les systèmes de neurotransmission cérébrale. Il est donc difficile d’identifier clairement les bases neurochimiques des différents effets psychotropes de l’alcool. D’autre part, la littérature scientifique confirme également le rôle des apprentissages par conditionnement dans le maintien de la consommation d’alcool et dans l’alcoolodépendance. Bien que l’importance des réponses conditionnées à l’éthanol est maintenant reconnue, les bases neurochimiques de ces effets conditionnés sont encore méconnues. Le présent travail est donc destiné à faire le point sur les connaissances actuelles des bases neurochimiques et comportementales de la consommation d’alcool et de l’addiction alcoolique. Plus particulièrement les neurotransmetteurs acides aminés ont fait l’objet d’investigations expérimentales destinées à élucider leur rôle dans les effets conditionnés à l’éthanol. [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 ▲]

The role of taurine in ethanol reinforcing effects

in Alcoholism, Clinical & Experimental Research (1998), 22

Taurine - a modulator of ethanol toxicity. From basic concepts to clinical reality

in Alcoholism, Clinical & Experimental Research (1998), 22

Changes in excitatory and inhibitory amino acids as a possible target for new treatments of alcoholism

in International Journal of Neuropsychopharmacology (1998), 1

Neurobiologie Comportementale de l'éthanol et de l'acétaldéhyde

in Alcoologie (1998), 20(4), 391-391

Acetaldehyde-induced changes in the monoamine and amino acid extracellular microdialysate content of the nucleus accumbens

in Neuropharmacology (1997), 36(2), 225-232

The effect of an acute intraperitoneal (i.p.) injection of acetaldehyde, 20 mglkg or 100mg/kg, on the microdialysate content of both amino acids and monoamine was studied in the nucleus accumbens (NA) by ... [more ▼]

The effect of an acute intraperitoneal (i.p.) injection of acetaldehyde, 20 mglkg or 100mg/kg, on the microdialysate content of both amino acids and monoamine was studied in the nucleus accumbens (NA) by a microdialysis technique. Acetaldehyde (ACH) which was detectable at levels of 50-130 µmol/g brain tissue 10 min after injection, evoked a significantd ecrease in the extracellular microdialysis dopamine content, which was sustained for the period of the study, i.e. 120 min. Homovanillicacid, HVA, decreased significantly when the lower dose of ACH was administered while dihydrophenylaceticacid, DOPAC, showed no significant change with either dose of ACH during the period of the study. Serotonin levels decreased significantly after both doses of acetaldehyde, with significant increases of its major metabolite, hydroxyindolacetic acid, 5-HIAA, with the higher acetaldehyde dose. Taurine increased significantly, only during the first twenty minutes, after both doses of acetaldehyde, although neither of the excitatory amino acids assayed, glutamate and aspartate, nor the inhibitoryamino acid, GABA, showed any significant changes. Acetaldehyde clearly evokes significant perturbation in the monoamine content of the NA, such changes being the converse to those reported for monoamine after ethanol administration, which might indicate a negative reinforcement effect. [less ▲]

Role of associative learning in the development of ethanol tolerance

in Alcohol & Alcoholism (1997), 32