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April 2018 - present
April 2018 - present
July 2007 - December 2008
Education
January 2002 - June 2017
Publications
Publications (44)
The Lewis (LEW) and Fischer 344 (F344) inbred rat strains are frequently used to study the role of genetic factors in vulnerability to drug addiction and relapse. Glutamate and γ-amino butyric acid (GABA) transmission are significantly altered after cocaine-induced reinstatement, although whether LEW and F344 rats differ in their accumbal glutamate...
Chronic exposure to cocaine induces modifications to neurons in the brain regions involved in addiction. Hence, we evaluated
cocaine-induced changes in the hippocampal CA1 field in Fischer 344 (F344) and Lewis (LEW) rats, 2 strains that have been
widely used to study genetic predisposition to drug addiction, by combining intracellular Lucifer yello...
Schedule-induced polydipsia (SIP) is an adjunctive behavior in which rats exhibit excessive drinking as a consequence of intermittent feeding, and it has been proposed as a candidate model to study the development of compulsive and repetitive behavior. Although several brain structures are involved in compulsive behavior, it has been suggested that...
We previously showed that cocaine self-administration increases spine density in CA1 hippocampal neurons in Lewis (LEW) but not in Fischer 344 (F344) rats. Dendritic spine morphology is intimately related to its function. Thus, we conducted a 3D morphological analysis of CA1 dendrites and dendritic spines in these two strains of rats. Strain-specif...
Derivatives from the Cannabis plant are the most commonly abused illegal substances in the world. The main psychoactive component found in the plant, Δ-9-tetrahydrocannabinol (THC), exerts its effects through the endocannabinoid system. Manipulations of this system affect some types of learning that seem to be dependent on dorsal striatum synaptic...
Rationale
Schedule-induced drinking (SID) is a behavioural phenomenon characterized by an excessive and repetitive drinking pattern with a distinctive temporal distribution that has been proposed as a robust and replicable animal model of compulsivity. Despite cannabis currently being the most widely consumed illicit drug, with growing interest in...
The hippocampus plays a key role in contextual conditioning and has been proposed as an important component of the cocaine addiction brain circuit. To gain knowledge about cocaine-induced alterations in this circuit, we used focused ion beam milling/scanning electron microscopy to reveal and quantify the three-dimensional synaptic organization of t...
The hippocampus plays a key role in contextual conditioning and has been proposed as an important component of the cocaine addiction brain circuit. To gain knowledge about cocaine-induced alterations in this circuit, we used Focused Ion Beam milling/Scanning Electron Microscopy (FIB/SEM) to reveal and quantify the 3D synaptic organization of the st...
Intermittent and excessive ethanol consumption over very short periods of time, known as binge drinking, is common in the adolescence, considered a vulnerable period to the effects of alcohol in terms of cognitive performance. One of the brain functions most drastically affected by ethanol in adolescent individuals seems to be spatial learning and...
Alcohol consumption during adolescence is deleterious to the developing brain and leads to persistent deficits in adulthood. Several results provide strong evidence for ethanol-associated alterations in glutamatergic signaling and impaired synaptic plasticity in the hippocampus. Protein phosphorylation is a well-known and well-documented mechanism...
Schedule-induced polydipsia (SIP) was established in spontaneously hypertensive rats (SHR), Wistar Kyoto rats (WKY), and Wistar rats, using a multiple fixed-time (FT) schedule of food delivery, with 30- and 90-s components. Thereafter, animals were exposed to methylphenidate (MPH; 2.5 mg/kg/d) for six consecutive SIP sessions. A test to assess poss...
Lewis (LEW) and Fischer 344 (F344) rats are considered a model of genetic vulnerability to drug addiction. We previously showed important differences in spatial learning and memory between them, but in contrast with previous experiments demonstrating cocaine-induced enhanced learning in Morris water maze (MWM) highly demanding tasks, the eight-arm...
The rodent parafascicular nucleus (PFn) or the centromedian-parafascicular complex of primates is a posterior intralaminar nucleus of the thalamus related to cortical activation and maintenance of states of consciousness underlying attention, learning and memory. Deep brain stimulation (DBS) of the PFn has been proved to restore arousal and conscio...
The spontaneously hypertensive rat (SHR) has been proposed as an animal model for attention deficit hyperactivity disorder (ADHD), and typically develops excessive patterns of response under most behavioural protocols. Schedule-induced polydipsia (SIP) is the excessive water consumption that occurs as a schedule effect when food is intermittently d...
Highly palatable foods behave as appetitive reinforcers and tend to be consumed compulsively. Nevertheless, the motivation for this kind of diets in experimental diet-induced obesity models has not been well established. Our hypothesis is that obesity caused by a regular consumption of high-fat diet (HFD) occurs concomitantly with the inhibition of...
La adicción al alcohol se presenta como un grave problema de salud pública y, en la actualidad, el consumo de esta droga se inicia a edades cada vez más tempranas. Se ha sugerido que la exposición repetida al alcohol durante la adolescencia provoca cambios duraderos en regiones del cerebro que controlan el aprendizaje pudiendo provocar alteraciones...
Posttraining intracranial self-stimulation (SS) in the lateral hypothalamus facilitates the acquisition and retention of several implicit and explicit memory tasks. Here, intracellular injections of Lucifer yellow were used to assess morphological changes in hippocampal neurons that might be specifically related to the facilitative posttraining SS...
Tradicionalmente, el estudio de la conducta de autoconsumo de drogas como operante en el laboratorio se ha realizado mediante procedimientos en los que el sujeto no tenía alternativas de elección. Otros estudios más recientes han añadido un componente de castigo positivo (la aparición de una descarga) asociado a la autoadministración, como una form...
Cocaine addiction alters synaptic plasticity in many brain areas involved in learning and memory processes, including the hippocampus. Long-term potentiation (LTP) is one of the best studied examples of hippocampal synaptic plasticity and it is considered as one of the molecular basis of learning and memory. We previously demonstrated that in the p...
The endocannabinoids anandamide and 2-arachidonyl glycerol (2-AG) are modulators of glutamate and γ-aminobutyric acid (GABA), two transmitters involved in cocaine addiction. However, little is known on the effects of cocaine on the enzymes that produce and degrade endocannabinoids. The present work addresses the effects of cocaine self-administrati...
The high rate of recidivism in cocaine addiction after prolonged periods of abstinence poses a significant problem for the effective treatment of this condition. Moreover, the neurobiological basis of this relapse phenomenon remains poorly understood. In this review, we will discuss the evidence currently available regarding the neurobiological cha...
E. Ambrosio1,∗, M. Miguéns1, N. del Olmo2, A. Higuera-Matas1,
C. García-Lecumberri1
1 Departmento de Psicobiologia, Universidad Nacional de Educación a
Distancia (UNED), Madrid, Spain, 2 Ciencias Farmaceúticas y de la
Alimentación, Universidad San Pablo-CEU, Boadilla del Monte,
Madrid, Spain
Cocaine is among the most widely abused central drug stim...
Lewis (LEW) and Fischer 344 (F344) rats differ in their response to drugs and are frequently used as an experimental model to study vulnerability to drug addiction. We have previously reported that significant differences in hippocampal synaptic plasticity exist between LEW and F344 rats after non-contingent chronic cocaine administration. However,...
Dose-response studies are thought to be a valuable tool to predict the most genetically drug-vulnerable individuals. However, dose-response curves for morphine self-administration have not yet been examined and nor strain differences might be evident. Therefore, this study aimed to define the dose-response curve for morphine self-administration (0....
Drug addiction results from the interplay between social and biological factors. Among these, genetic variables play a major role. The use of genetically related inbred rat strains that differ in their preference for drugs of abuse is one approach of great importance to explore genetic determinants. Lewis and Fischer 344 rats have been extensively...
In a previous work, we have shown that chronic administration of the cannabinoid agonist CP 55,940 (CP) during periadolescence increases cocaine self-administration in adult female rats, while it produces no such effect in males (Higuera-Matas et al., 2008). To extend these findings, we have analysed here the brains of the rats used as subjects in...
Purpose To analyze brain metabolic response to acute cocaine in male and female Wistar rats with or without a history of cannabinoid
exposure during periadolescence.
Procedures The synthetic cannabinoid agonist CP 55,940 (CP) or its vehicle (VH), were administered to male and female rats during periadolescence.
When these animals reached adulthood...
Purpose:
To analyze brain metabolic response to acute cocaine in male and female Wistar rats with or without a history of cannabinoid exposure during periadolescence.
Procedures:
The synthetic cannabinoid agonist CP 55,940 (CP) or its vehicle (VH), were administered to male and female rats during periadolescence. When these animals reached adult...
Pubertal and adolescent exposure to cannabinoids is associated with enduring alterations in anxiety and memory. However, periadolescence virtually remains unexplored. Here, we measured anxiety in the Elevated Plus Maze (EPM) in adult Wistar rats treated at periadolescence (P28-P38) with the cannabinoid agonist CP 55,940 (CP) (0.4 mg/kg; 2 ml/kg i.p...
The Lewis (LEW) and Fischer 344 (F344) rat strains have been used as a model to study genetic vulnerability to drug addiction and they differ in their dopaminergic systems. We have studied the variation in the D1-like and D2-like receptors in distinct brain regions of LEW and F344 rats that self-administered morphine (1 mg/kg) for 15 days and also...
Although dopamine and glutamate transmission has been implicated in cocaine dependence, the effects of the extinction of cocaine self-administration on protein transporters in both of these neurotransmitter systems remain unknown. We have used a yoked-box procedure to simultaneously test rats in triads, one rat that actively self-administered cocai...
Repeated administration of drugs of abuse is thought to induce a variety of persistent changes in both behavior and brain morphology, including modifications of neurons from the brain regions involved in addiction. We have studied the morphology of the basal dendritic arbor of cortical pyramidal neurons in addiction-resistant Fischer 344 strain rat...
Marijuana consumption during adolescence has been proposed to be a stepping-stone for adult cocaine addiction. However, experimental evidence for this hypothesis is missing. In this work we chronically injected male and female Wistar rats with either the cannabinoid agonist CP 55,940 (CP; 0.4 mg/kg) or its corresponding vehicle. Adult acquisition (...
Long-term potentiation (LTP) is considered to be a cellular substrate of learning and memory. Indeed, the involvement of LTP-like mechanisms in spatial learning has consistently been demonstrated in the Morris water maze test. We have previously shown that hippocampal LTP in Lewis rats was modulated by cocaine self-administration, although the perf...
Lewis (LEW) and Fischer 344 (F344) rats show differential morphine self-administration rates. In this study, after animals of both strains self-administered morphine (1mg/kg) or extinguished this behaviour for 3, 7 or 15days, we measured the binding to, and functional state of mu opioid receptors (MORs) as well as proenkephalin (PENK) mRNA content...
The consumption of drugs of abuse provokes sensitization, the development of tolerance, dependency, and eventually addiction. It is thought that these events are partially a consequence of drug-induced alterations in the organization of neuronal circuits in specific areas of the brain. In the present study, we have used intracellular injections of...
Drug addiction may involve learning and memory processes requiring the participation of hippocampal formation. One of the best studied examples of hippocampal synaptic plasticity is the long-term potentiation (LTP) which usually occurs when hippocampal synapses are stimulated with high-frequency stimulation. The aim of this work has been to study t...
Previously, we have shown that long-term potentiation (LTP) in hippocampus of Lewis rats was significantly modulated by cocaine self-administration. Using a single train of high-frequency stimulation of 100 Hz for 1s (HFS), we found an enhancement of LTP after cocaine self-administration that was maintained even during the extinction of this behav...