Maria Jose Cano-Cebrián

• Professor
• Lecturer at University of Valencia

The alcohol use disorder (AUD) is a complex, chronic pathology with a high relapse rate. Resumption to alcohol intake after a long period of abstinence is one of the most severe handicaps of this pathological condition. Consequently, in the last decade, a wealth of studies has focused on the neurobiological mechanisms involved in various phases of...

Rationale Opioid drugs indirectly activate dopamine (DA) neurons in the ventral tegmental area (VTA) through a disinhibition mechanism mediated by mu opioid receptors (MORs) present both on the GABA projection neurons located in the medial tegmental nucleus/tail of the VTA (RMTg/tVTA) and on the VTA GABA interneurons. It is well demonstrated that e...

Rationale Using a preclinical model based on the Alcohol Deprivation Effect (ADE), we have reported that N-Acetylcysteine (NAC) can prevent the relapse-like drinking behaviour in long-term ethanol-experienced male rats. Objectives To investigate if chronic ethanol intake and protracted abstinence affect several glutamate transporters and whether N...

Chemotherapy causes intestinal mucositis, which includes villous atrophy and altered mucosal barrier function. However, there is an uncertainty regarding how the reduced small-intestinal surface area affects the mucosal permeability of the small marker probe mannitol (MW 188), and how the mucosa responds to luminal irritants after chemotherapy. The...

Rationale Accumulating evidence suggests that chronic alcohol consumption is associated with excessive oxidative damage and neuroinflammatory processes and these events have been associated to early alcohol withdrawal. In the present research we wonder if brain oxidative stress and neuroinflammation remains altered during prolonged withdrawal situa...

N-acetylcysteine (NAC) is a prodrug that is marketed as a mucolytic agent and used for the treatment of acetaminophen overdose. Over the last few decades, evidence has been gathered that suggests the potential use of NAC as a new pharmacotherapy for alcohol use disorder (AUD), although its mechanism of action is already being debated. In this paper...

Alcohol use disorders are chronic and highly relapsing disorders, thus alcoholic patients have a high rate of recidivism for drug use even after long periods of abstinence. The literature points to the potential usefulness of N‐acetylcysteine (NAC) in the management of several substance use disorders probably due to its capacity to restore brain ho...

A healthy intestinal barrier prevents uptake of allergens and toxins, whereas intestinal permeability increases following chemotherapy and in many gastrointestinal and systemic diseases and disorders. Currently, there are no approved drugs that target and repair the intestinal epithelial barrier while there is a medical need for such treatment in g...

Sufficient colonic absorption is necessary for all systemically acting drugs in dosage forms that release the drug in the large intestine. Preclinically, colonic absorption is often investigated using the rat single-pass intestinal perfusion model. This model can determine intestinal permeability based on luminal drug disappearance, as well as the...

Ethanol, as other drugs of abuse, is able to activate the ventral tegmental area dopamine (VTA-DA) neurons leading to positively motivational alcohol-seeking behavior and use, and, ultimately to ethanol addiction. In the last decades, the involvement of brain-derived acetaldehyde (ACD) in the ethanol actions in the mesolimbic pathway has been widel...

The nigrostriatal dopamine system is implicated in the regulation of reward and motor activity. Dopamine (DA) release in dorsal striatum (DS) is controlled by the firing rate of DA neurons in substantia nigra pars compacta. However, influences at terminal level, such as those involving activation of mu opioid receptors (MORs), can play a key role i...

In previous investigations, we demonstrated that D-penicillamine (DP), a sulfhydryl aminoacid which has been studied as sequestration agent of acetaldehyde (ACD), is able to prevent the alcohol deprivation effect (ADE) but not voluntary ethanol consumption. Both results were obtained in long-termethanol-experienced Wistar rats. Based on a previous...

Experimental evidence has demonstrated that the reinforcing effects of ethanol crucially depend on the brain formation of acetaldehyde (ACD). Rationally supported by this basis, we previously evaluated a novel strategy to prevent relapse in alcoholism based on chemical ACDinactivation using D-Penicillamine (DP). Under our experimental conditions, t...

Previous electrophysiological and behavioral data have revealed the existence of ethanol opposite effects (excitatory and inhibitory) on the posterior ventral tegmental area (pVTA) dopamine (DA) neurons activity. These activating and depressing effects of ethanol could be the result of two concurrent and opposing mechanisms, one increasing and the...

Pharmacokinetic studies concerning D-penicillamine (an acetaldehyde sequestering agent) are scarce and have not evaluated the influence of chronic ethanol consumption and age on its disposition. Since recent preclinical studies propose D-penicillamine as a promising treatment for alcohol relapse, the main aim of the present work was to evaluate the...

Opioid antagonists are licensed drugs for treating alcohol use disorders; nonetheless, clinical studies have evidenced their limited effectiveness. Preclinical findings indicate that opioid receptor (OR) antagonists, such as naltrexone (NTX), reduce the alcohol deprivation effect (ADE). However, a detailed analysis of published data shows the exist...

The pharmacokinetics of acamprosate were examined in the rat after oral and intravenous administration in order to detect the possible presence of a flip-flop phenomenon. Rats received 9.3 or 73.3 mg/kg of the drug as an intravenous bolus. The same doses were orally administered via gastric intubation. Plasma samples were taken from the jugular vei...

Recently, we have shown that D1 and D2 receptors in the ventral hippocampus (VH) modulate both the locomotor activation and the increase in dopamine (DA) levels in the rat nucleus accumbens (NAc) induced by NMDA stimulation of the VH. In the present study we analyze the possible role of VH D1 and D2 receptors in the modulation of the cFos expressio...

A number of studies have shown that chemical stimulation (using N-methyl-D-aspartate (NMDA) infusions) or electrical stimulation of the ventral hippocampus (VH) elicits locomotor activation and sustained increases in nucleus accumbens (NAc) dopamine (DA) levels in rodents. How DA neurotransmission in NAc is involved in these effects has also been w...

This paper reviews the empirical methods of quantitative microdialysis that have been used to interpret the results obtained from pharmacokinetic studies. The concept of extraction efficiency or recovery and the properties of recovery in vivo (variation with flow rate, time dependency and influence of the mode of administration) are considered. The...

Peroral delivery of hydrophilic drugs is one of the greatest challenges in biopharmaceutical research. Hydrophilic drugs usually present low bioavailability after oral administration. One of the causes of this low bioavailability is their poor intestinal permeation through the paracellular pathway. This pathway is actually restricted by the presenc...

The purpose of this study was to explore the intestinal absorption mechanism of acamprosate and to attempt to improve the bioavailability (BA) of the drug through modulation of its intestinal absorption using two enhancers (polysorbate 80 and sodium caprate) based on in situ, in vitro and in vivo models and comparing the results obtained. Intestina...

Recently, we have shown that acamprosate is able to modulate extracellular dopamine (DA) levels in the nucleus accumbens (NAc) and may act as an antagonist of N-methyl-D-aspartate (NMDA) receptors. Neurochemical studies show that chemical stimulation (using NMDA) of the ventral subiculum (vSub) of the hippocampus produces robust and sustained incre...

The effects of acamprosate on the in vivo dopamine extracellular levels in the nucleus accumbens and the involvement of N-methyl-D-aspartate (NMDA) receptors in these effects were investigated. Microdialysis in freely moving rats was used to assess dopamine levels before and during simultaneous perfusion of acamprosate and/or different agonists or...

In the last years important advances have been made in the development of drugs for the treatment of alcohol addiction. Acamprosate (calcium bis-acetylhomotaurine) is one of the better established drugs in this field on the European market. This review focuses first on the pharmacokinetics of acamprosate. The published data and the recent advances...

The multiple pharmaceutical applications of chitosans have been reviewed in this paper. After describing its structure and physico-chemical properties, an overview of the use of this polymer in controlled release dosage forms as well as in other dosage forms to improve bioavailability and safety has been made. Furthermore, the capacity of chitosan...