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It is well known the depressor effect of alcohol on several inhibitory nervous centres. This can be due to the inhibition that induces in the release of different type of neurotransmitters, and because alcohol can increase the membrane fluidity and changes the function of proteins inserted in the membrane. Several aminopeptidases (AP) have been described as enzymes that regulate the activity of peptide neurotransmitters. In the present work, the influence of alcohol (25, 50 and 100 mM) on several aminopeptidase activities (alanyl AP, arginyl AP, cystinyl AP, leucyl AP and tyrosyl AP) has been determined in synaptosomes obtained from the cortex of mouse, under basal and K+ stimulated conditions and their calcium dependence, in a non toxic in vitro model.AP activities were determined using aminoacyl ? naphthylamides as substrates. Non toxic in vitro model were demonstrated analyzing free radical generation, lipid peroxidation and oxidation of synaptosomal proteins. In addition, the bioenergetic behavior of synaptosomes was determined under different experimental protocols.In basal conditions, alcohol produces a dose related inhibition of alanyl AP activity. The rest of activities show a biphasic behavior. In this way, depending on the concentration of alcohol used, aminopeptidases are inhibited or stimulated. Depolarization with K+ 25 mM leads to a decrease of alanyl AP and tyrosyl AP activities but does not change the rest of activities. The presence of alcohol under stimulated conditions produces the inhibition of all the enzymatic activities, specially with the highest concentrations used.Alcohol modifies several aminopeptidase activities from synaptosomes of the cortex of mouse, acting in different ways under basal or stimulated conditions. These effects seem not to be related with degenerative events induced by alcohol. Therefore, a specific effect of this substance on the neurotransmisory/neuromodulatory systems mediated by neuropeptides must exist, modifying the enzymes that are responsible of their degradation.

It is well known the depressor effect of alcohol on several inhibitory nervous centres. This can be due to the inhibition that induces in the release of different type of neurotransmitters, and because alcohol can increase the membrane fluidity and changes the function of proteins inserted in the membrane. Several aminopeptidases (AP) have been described as enzymes that regulate the activity of peptide neurotransmitters. In the present work, the influence of alcohol (25, 50 and 100 mM) on several aminopeptidase activities (alanyl AP, arginyl AP, cystinyl AP, leucyl AP and tyrosyl AP) has been determined in synaptosomes obtained from the cortex of mouse, under basal and K+ stimulated conditions and their calcium dependence, in a non toxic in vitro model.AP activities were determined using aminoacyl ? naphthylamides as substrates. Non toxic in vitro model were demonstrated analyzing free radical generation, lipid peroxidation and oxidation of synaptosomal proteins. In addition, the bioenergetic behavior of synaptosomes was determined under different experimental protocols.In basal conditions, alcohol produces a dose related inhibition of alanyl AP activity. The rest of activities show a biphasic behavior. In this way, depending on the concentration of alcohol used, aminopeptidases are inhibited or stimulated. Depolarization with K+ 25 mM leads to a decrease of alanyl AP and tyrosyl AP activities but does not change the rest of activities. The presence of alcohol under stimulated conditions produces the inhibition of all the enzymatic activities, specially with the highest concentrations used.Alcohol modifies several aminopeptidase activities from synaptosomes of the cortex of mouse, acting in different ways under basal or stimulated conditions. These effects seem not to be related with degenerative events induced by alcohol. Therefore, a specific effect of this substance on the neurotransmisory/neuromodulatory systems mediated by neuropeptides must exist, modifying the enzymes that are responsible of their degradation.

Human genetic variation in the nicotinic receptor gene cluster CHRNA5/A3/B4, in particular the non-synonymous and frequent CHRNA5 variant rs16969968 (α5SNP), has an important consequence on smoking behavior in humans. A number of genetic association studies have additionally implicated the CHRNA5 gene in addictions to other drugs, and also body mass index (BMI). Here, we model the α5SNP, in a transgenic rat line, and establish its role in alcohol dependence, and feeding behavior. Rats expressing the α5SNP consume more alcohol, and exhibit increased relapse to alcohol seeking after abstinence. This high-relapsing phenotype is reflected in altered activity in the insula, linked to interoception, as established using c-Fos immunostaining. Similarly, relapse to food seeking is increased in the transgenic group, while a nicotine treatment reduces relapse in both transgenic and control rats. These findings point to a general role of this human polymorphism in reward processing, and multiple addictions other than smoking. This could pave the way for the use of medication targeting the nicotinic receptor in the treatment of alcohol use and eating disorders, and comorbid conditions in smokers.

Human genetic variation in the nicotinic receptor gene cluster CHRNA5/A3/B4, in particular the non-synonymous and frequent CHRNA5 variant rs16969968 (α5SNP), has an important consequence on smoking behavior in humans. A number of genetic association studies have additionally implicated the CHRNA5 gene in addictions to other drugs, and also body mass index (BMI). Here, we model the α5SNP, in a transgenic rat line, and establish its role in alcohol dependence, and feeding behavior. Rats expressing the α5SNP consume more alcohol, and exhibit increased relapse to alcohol seeking after abstinence. This high-relapsing phenotype is reflected in altered activity in the insula, linked to interoception, as established using c-Fos immunostaining. Similarly, relapse to food seeking is increased in the transgenic group, while a nicotine treatment reduces relapse in both transgenic and control rats. These findings point to a general role of this human polymorphism in reward processing, and multiple addictions other than smoking. This could pave the way for the use of medication targeting the nicotinic receptor in the treatment of alcohol use and eating disorders, and comorbid conditions in smokers.

Involvement of N-methyl-D-aspartate (NMDA) receptor complex and 5-hydroxytryptamine3 (5-HT3) receptors in state-dependent learning (SDL) induced by ethanol (EtOH) was investigated in the step-through passive avoidance task in rats. Pre-training injections of EtOH or MK-801 reduced step-through latency in the test session conducted 24 h after the training session. Pre-test as well as pre-training injections of EtOH failed to reduce the latency, while pre-training and pre-test injections of MK-801 reduced the latency. These results show that EtOH but not MK-801 produces SDL. SDL induced by EtOH was blocked by ICS205-930 injected before either the training or test session. However, ICS205-930 failed to block SDL induced by diazepam and muscimol. These results suggest that NMDA receptor complex may not be involved in SDL, and that 5-HT3 receptors may contribute to SDL induced by EtOH but not by diazepam and muscimol.

Involvement of N-methyl-D-aspartate (NMDA) receptor complex and 5-hydroxytryptamine3 (5-HT3) receptors in state-dependent learning (SDL) induced by ethanol (EtOH) was investigated in the step-through passive avoidance task in rats. Pre-training injections of EtOH or MK-801 reduced step-through latency in the test session conducted 24 h after the training session. Pre-test as well as pre-training injections of EtOH failed to reduce the latency, while pre-training and pre-test injections of MK-801 reduced the latency. These results show that EtOH but not MK-801 produces SDL. SDL induced by EtOH was blocked by ICS205-930 injected before either the training or test session. However, ICS205-930 failed to block SDL induced by diazepam and muscimol. These results suggest that NMDA receptor complex may not be involved in SDL, and that 5-HT3 receptors may contribute to SDL induced by EtOH but not by diazepam and muscimol.

Recent electrophysiological evidence suggests that ethanol simultaneously exerts opposite effects on the activity of dopamine (DA) neurons in the ventral tegmental area (VTA) through two parallel mechanisms, one promoting and the other reducing the GABA release onto VTA DA neurons. Here we explore the possible behavioural implications of these findings by investigating the role displayed by acetaldehyde (the main metabolite of ethanol) and the non-metabolized fraction of ethanol in motor activity of rats. We analyse the appearance of motor activation or depression after intra-VTA administration of ethanol in rats subjected to different pharmacological pre-treatments designed to preferentially test either the effects of acetaldehyde or the non-metabolized ethanol. Motor activity was evaluated after intra-VTA administration of 35 nmol of ethanol, an apparently ineffective dose that does not modify the motor activity of animals. Pharmacological pre-treatments were used in order to either increase (cyanamide, 10 mg/kg, ip) or decrease (D-penicillamine, 50 mg/kg, ip and sodium azide, 7 mg/kg, ip) acetaldehyde levels in the VTA. Pre-treatments aimed to augment acetaldehyde, increased motor activity of rats. Otherwise, pre-treatments intended to decrease local acetaldehyde levels evoked significant reductions in motor activity that were prevented by the local blockade (bicuculline, 17.5 pmol) of the GABAA receptors. Our findings suggest that the brain-generated acetaldehyde is involved in the stimulant effects of ethanol, whereas the non-biotransformed fraction of ethanol, acting through the GABAA receptors, would account for the depressant effects. The present behavioural findings suggest that ethanol dually modulates the activity of DA neurons.