Fetal alcohol programming of subsequent alcohol affinity: A reviewb ased on preclinical, clinical and epidemiological studies

The anatomo-physiological disruptions inherent to different categories of the Fetal Alcohol Spectrum Disorder do not encompass all the negative consequences derived from intrauterine ethanol (EtOH) exposure. Preclinical, clinical and epidemiological studies show that prenatal EtOH exposure also results in early programming of alcohol affinity. This affinity has been addressed through the examination of how EtOH prenatally exposed organisms recognize and prefer the drug´s chemosensory cues and their predisposition to exhibit heightened voluntary EtOH intake during infancy and adolescence. In altricial species these processes are determined by the interaction of at least three factors during stages equivalent to the 2nd and 3rd human gestational trimester: (i) fetal processing of the drug´s olfactory and gustatory attributes present in the prenatal milieu; (ii) EtOH´s recruitment of central reinforcing effects that also imply progressive sensitization to the drug´s motivational properties; and (iii) an associative learning process involving the prior two factors. This Pavlovian learning phenomenon is dependent upon the recruitment of the opioid system and studies also indicate a significant role of EtOH´s principal metabolite (acetaldehyde, ACD) which is rapidly generated in the brain via the catalase system. The central and rapid accumulation of this metabolite represents a major factor involved in the process of fetal alcohol programming. According to recent investigations, it appears that ACD exerts early positive reinforcing consequences and antianxiety effects (negative reinforcement). Finally, this review also acknowledges human clinical and epidemiological studies indicating that moderate and binge-like drinking episodes during gestation result in neonatal recognition of EtOH´s chemosensory properties coupled with a preference towards these cues. As a whole, the studies under discussion emphasize the notion that even subteratogenic EtOH exposure during fetal life seizes early functional sensory and learning capabilities that pathologically shape subsequent physiological and behavioral reactivity towards the drug.Fil: Miranda Morales, Roberto Sebastián. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; ArgentinaFil: D'aloisio, Génesis. Universidad Nacional de Córdoba. Facultad de Psicología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; ArgentinaFil: Anunziata, Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; ArgentinaFil: Abate, Paula. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; ArgentinaFil: Molina, Juan Carlos. Universidad Nacional de Córdoba. Instituto de Investigaciones Psicológicas. - Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones Psicológicas; Argentin

Reclutamiento de procesos de aprendizaje a nivel fetal a través de la intoxicación etílica: Programación de la apetencia hacia la droga y de disrupciones en la plasticidad respiratoria

El etanol durante el embarazo ejerce efectos teratogénicos; en otras palabras, la droga más consumida en el mundo posee la capacidad de inducir o aumentar la incidencia de malformaciones congénitas cuando se administra o actúa durante la organogénesis. El Espectro de Desordenes Fetales del Alcohol incluye una serie de alteraciones anatomo-fisiológicas que ponen en peligro el desarrollo del individuo prenatalmente expuesto a la droga. Sin embargo, este rango de malformaciones y consecuencias negativas a nivel neurocomportamental no incluye aun a los fenómenos de programación fetal respecto a la afinidad hacia la droga y en relación a los trastornos funcionales que impactan sobre la neuroplasticidad respiratoria. Como será discutido en el presente simposio, ambos fenómenos están íntimamente ligados a tempranos procesos de aprendizaje derivados de la exposición a la droga. Al aunar la literatura preclínica, clínica y epidemiológica, se observa que infantes y adolescentes prenatalmente expuestos al psicotrópico, exhiben una marcada predisposición a consumir la droga. En especies altriciales incluyendo la humana, esta afinidad etílica ha sido corroborada al examinar el reconocimiento y la preferencia hacia atributos olfato-gustativos de la droga y patrones de consumo voluntario de la misma en función de la exposición etílica prenatal. Recientes investigaciones de orden preclínicas, realizadas durante periodos ontogénicos análogos al segundo y tercer trimestres de gestación humana, han enfatizado la noción que la programación de la apetencia etílica está determinada por la interacción de al menos tres factores. Los mismos son: (i) el procesamiento fetal de los atributos quimiosensiorales de la droga que están presentes en el contexto intrauterino, (ii) el reclutamiento etílico de efectos reforzantes a nivel cerebral que también implica una progresiva sensibilización hacia la propiedades motivacionales de la droga y (iii) un proceso de aprendizaje asociativo derivado de la contingencia entre los dos primeros factores antes mencionados. Este fenómeno de aprendizaje Pavloviano es dependiente del reclutamiento del sistema opioidérgico cerebral. El mismo modula tanto la sensibilidad hacia las aristas reforzantes positivas de la droga como en referencia a sus propiedades reforzantes negativas; en otros términos, su acción ansiolítica. Asimismo, los estudios indican un significativo rol del principal metabolito del etanol (acetaldehído) que rápidamente se genera y acumula en el cerebro a través de la acción metabólica del sistema de catalasas cerebral. Recientes investigaciones indican que este metabolito desencadena tempranos efectos reforzantes positivos e incluso procesos de orden ansiolíticos. En forma concomitante con estos procesos de orden motivacionales, el etanol y el acetaldehído, ejercen efectos depresores sobre la respiración fetal y neonatal. Estudios preclínicos y clínicos indican que la neuroplasticidad respiratoria derivada de la exposición temprana al psicotrópico también es dependiente de procesos de aprendizaje no asociativos (sensibilización) y asociativos. En su conjunto, los estudios aquí presentados enfatizan la noción que, incluso al considerarse dosis subteratogénicas del etanol, la experiencia temprana con el psicotrópico recluta tempranas capacidades sensoriales y de aprendizaje que programan patológicamente al organismo en términos de su reactividad fisiológica y comportamental hacia la droga.Fil: Macchione, Ana Fabiola. Universidad Nacional de Córdoba. Instituto de Investigaciones Psicológicas. - Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones Psicológicas; Argentina. Universidad Nacional de Córdoba. Facultad de Psicología; ArgentinaFil: Anunziata, Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; ArgentinaFil: Abate, Paula. Universidad Nacional de Córdoba. Facultad de Psicología; Argentina. Universidad Nacional de Córdoba. Instituto de Investigaciones Psicológicas. - Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones Psicológicas; ArgentinaFil: Molina, Juan Carlos. Universidad Nacional de Córdoba. Facultad de Psicología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; ArgentinaXVIII Reunión Nacional; VII Encuentro Internacional de la Asociación Argentina de Ciencias del ComportamientoMar del PlataArgentinaAsociación Argentina de Ciencias del ComportamientoInstituto de Psicología Básica, Aplicada y TecnologíaUniversidad Nacional de Mar del Plat

Sensitization to ethanol’s disruptive effects upon early breathing plasticity associated with hypoxia and hypercapnia

Ethanol (EtOH) consumption during pregnancy and lactation represents a risk factor related with the Sudden Infant Death Syndrome (SIDS). This phenomenon has promoted research linking prenatal EtOH effects on the respiratory system during early ontogeny. It should also be noted that prolonged episodes of neonatal respiratory depression represent a risk factor in terms of hypoxic-ischemic effects with negative consequences on brain development. In a first study during postnatal day (PD) 9 we analyzed the impact of different doses of EtOH (0.0, 0.75, 1.37 or 2.0 g/kg) upon the respiratory response and the potential psychomotor effects in pup rats pre-exposed or not to 2.0 g/kg of EtOH during PDs 3-7. At PD 9 animals were also subjected to sequential air conditions defined as initial normoxia, hypoxia and recovery normoxia. In a second study we analyzed the blood of animals only exposed to 0.0 or 2.0g/kg of EtOH during PDs 3-9 (not subjected to a hypoxic event). The aim was to examine if mere intoxication with a moderate dose of EtOH is capable of modifying blood metabolic patterns associated with hypoxia or hypercapnia. In the first study during PDs 3-7 EtOH exerted a depressant effect upon breathing frequencies. These animals also showed a progressive sensitization effect relative to the depressant effects of the drug and lesser levels of apneas. At PD 9 dose dependent respiratory depressions were observed when pups were challenged with a hypoxic event. Independently from prior experience with EtOH, drug treatment at PD 9 significantly disrupted respiratory frequencies particularly during the hypoxic and the recovery normoxia phases. Respiratory disorders triggered by these air conditions have been implicated in the pathophysiology of SIDS. These results show that breathing plasticity is disrupted during a critical stage where respiratory alterations may lead to hypoxiaassociated syndromes that endanger brain development. In terms of psychomotor activity, animals exposed to 2.0 g/kg of EtOH at PD 9 showed heightened duration and frequency of grooming. In the second study animals exposed at least one time to EtOH exhibited lower pH and higher CO2 than animals that were never exposed to EtOH. This results suggest metabolic acidosis probably due to EtOH-related hypercapnia during a vulnerable stage in development relative to SIDS.Fil: Anunziata, Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; ArgentinaFil: Macchione, Ana Fabiola. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; Argentina. Universidad Nacional de Córdoba. Instituto de Investigaciones Psicológicas. - Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones Psicológicas; ArgentinaFil: Angulo Alcalde, Asier. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; ArgentinaFil: Trujillo, María Verónica. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; ArgentinaFil: Wille-bille, Aranza. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; ArgentinaFil: Amigone, José Luis. Hospital Privado de Córdoba. Laboratorio de Bioquímica Clínica; ArgentinaFil: Molina, Juan Carlos. Universidad Nacional de Córdoba. Facultad de Psicología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; ArgentinaIX LASBRA International Meeting: Determinants of Alcoholism: bridging the gap between epidemiologic and basic researchCórdobaArgentinaLatin American Society for Biomedical Research on Alcoholis

Consumo de alcohol durante el embarazo

Comentario relativo a las categorias diagnósticas de la problemática del alcohol durante el embarazo. Especial énfasis en consecuencias del consumo moderado de etanol y los aspectos de programación fetal con la droga.Fil: Ahumada, Luis A.. Gobierno de la Provincia de Cordoba. Hospital Misericordia Nuevo Siglo; ArgentinaFil: Anunziata, Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; ArgentinaFil: Molina, Juan Carlos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; Argentina. Universidad Nacional de Córdoba. Facultad de Psicología; Argentin

Birth Defects Associated with Prenatal Alcohol Exposure-A Review.

Since the recognition of fetal alcohol syndrome, alcohol has been accepted as a human teratogen. However, little is known about the relation between prenatal alcohol exposure and the spectrum of associated major birth defects. The objective of this review was to summarize data on the association of major congenital abnormalities and prenatal alcohol exposure. We included all major birth defects according to ICD-10 classification. We found that the strongest evidence to date lies in the research examining herniation (gastroschisis and omphalocele), oral clefts (cleft lip with or without palate and cleft palate) and cardiac defects. There is less consistent evidence supporting the association between prenatal alcohol exposure and anomalies of gastrointestinal system, diaphragmatic hernia, genitourinary system and neural tube defects. We found no material support for PAE and choanal atresia, biliary atresia or clubfoot

Ethanol-Related Learning in Rat Neonates Impact upon Apneic Episodes and Promote Seeking Behavior of Stimuli that Signaled the State of Intoxication

In rats, high ethanol doses during early postnatal life exert deleterious effects upon brain development that impact on social and cognitive abilities. This stage in development partially overlaps with the 3rd human gestational trimester in terms of synaptogenesis. At this stage, human fetuses and rat neonates (postnatal days 3-9) exhibit relatively high respiratory rates that are affected by subteratogenic ethanol doses. Recent studies suggest conditioned breathing responses in the developing organism given explicit associations between exteroceptive stimuli and the state of EtOH intoxication. The present study was meant to analyze how apneic episodes are affected by the drug itself or through learning processes involving this psychotropic agent. During PDs 3, 5, 7 and 9 rats were subjected to differential experiences with salient tactile cues explicitly paired or not with the effects of vehicle or EtOH (2.0 g/kg) intragastric administration. A tactile discrimination paradigm applied during PDs 3, 5, 7 and 9 was conducted under stressful circumstances (maternal deprivation, exposure to a novel environment and drug administration procedure) for the developing organism. Pups were individually tested in a whole body plethysmograph where a given tactile cue was presented under the state of sobriety while an alternative texture was associated with the state of intoxication. Ethanol intoxication systematically inhibited the occurrence of apneic episodes. Most importantly, it was observed that tactile cues (either smooth or rough) systematically paired with ethanol intoxication also promoted inhibitory effects upon the emergence of apneas (isodirectional conditioned response). The study also revealed that ethanol also results in a sensitization process relative to its inhibitory effects upon apneic episodes. At PD11, pups were tested in a two-way tactile preference test defined by the textures previously experienced. This test revealed that ethanol intoxication increased preferences towards the stimuli that predicted such a toxic state. These last results may imply both the systematically reported positive reinforcing effects of ethanol during early ontogeny and/or its negative reinforcement capability in terms of antianxiety effects. As a whole these results emphasize the need to consider ethanol’s motivational effects during early development upon the regulation of breathing patterns and subsequent affinity for the drug.Fil: D'aloisio, Génesis. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; ArgentinaFil: Anunziata, Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; ArgentinaFil: Acevedo, María Belén. University of Illinois; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Macchione, Ana Fabiola. Universidad Nacional de Córdoba. Facultad de Psicología; Argentina. Universidad Nacional de Córdoba. Instituto de Investigaciones Psicológicas. - Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones Psicológicas; ArgentinaFil: Molina, Juan Carlos. Universidad Nacional de Córdoba. Facultad de Psicología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; ArgentinaIX LASBRA International Meeting; Latin American Society for Biomedical Research on AlcoholismCórdobaArgentinaLatin American Society for Biomedical Research on Alcoholis

Early Ethanol Preexposure Modifies Expression of the 5HT2A Receptor Promoting Long-Term Breathing Plasticity in Neonate Rats

EtOH´s effects upon respiration are attributed to central respiratory network disruptions, especially in the medullary serotonin (5HT) system. 5HT2A/2C receptors are involved in the reduction of the phrenic nerve activity and breathing depression. We hypothesize that early EtOH preexposure alters neonatal respiration through the 5HT system´s plasticity. Here, we evaluated breathing rates and the relative expression of 5HT 2A and 2C receptors in the brainstem as a function of EtOH preexposure in neonates. Pups received i.g administrations of 2.0 or 0.0g/kg EtOH at postnatal days (PD) 3, 5 and 7. At PD 9, breathing frequencies were recorded under normoxia or hypoxia. Brainstems were collected to quantified relative mRNA expression of 5HT 2A and 2C receptors, by qPCR. Under normoxia, EtOH preexposed pups (preEtOH) exhibited high 5HT2A expression levels and breathing depressions. An opposite phenomenon was observed in preEtOH pups tested under hypoxia. An exacerbated hyperventilation associated with low 5HT2A expression levels was found. No significant differences were found in 5HT2C expression levels. These results together with our previous findings that show changes in the raphe obscurus activation patterns, suggest that a brief EtOH preexposure is enough to induce 5HT system?s plasticity, disturbing neonatal breathing. The 5HT components mismatch may be associated with breathing disruptions commonly observed in human neonates, such as Sudden Infant Death Syndrome.Fil: Macchione, Ana Fabiola. Universidad Nacional de Córdoba. Instituto de Investigaciones Psicológicas. - Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones Psicológicas; ArgentinaFil: Anunziata, Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; ArgentinaFil: Sahonero, Milagros. Universidad Nacional de Córdoba. Facultad de Psicología; ArgentinaFil: Trujillo, Verónica. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; ArgentinaFil: Molina, Juan Carlos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; ArgentinaXXXIV Reunión Anual de la Sociedad Argentina de NeurocienciasVilla Carlos PazArgentinaSociedad Argentina de Investigación en Neurociencia

Brief ethanol exposure and stress-related factors disorganize neonatal breathing plasticity during the brain growth spurt period in the rat

Rationale: The effects of early ethanol exposure upon neonatal respiratory plasticity have received progressive attention given a multifactorial perspective related with sudden infant death syndrome or hypoxia-associated syndromes. The present preclinical study was performed in 3–9-day-old pups, a stage in development characterized by a brain growth spurt that partially overlaps with the 3rd human gestational trimester. Methods: Breathing frequencies and apneas were examined in pups receiving vehicle or a relatively moderate ethanol dose (2.0 g/kg) utilizing a whole body plethysmograph. The experimental design also considered possible associations between drug administration stress and exteroceptive cues (plethysmographic context or an artificial odor). Ethanol exposure progressively exerted a detrimental effect upon breathing frequencies. A test conducted at PD9 when pups were under the state of sobriety confirmed ethanol’s detrimental effects upon respiratory plasticity (breathing depression). Results: Pre-exposure to the drug also resulted in a highly disorganized respiratory response following a hypoxic event, i.e., heightened apneic episodes. Associative processes involving drug administration procedures and placement in the plethysmographic context also affected respiratory plasticity. Pups that experienced intragastric administrations in close temporal contiguity with such a context showed diminished hyperventilation during hypoxia. In a 2nd test conducted at PD9 while pups were intoxicated and undergoing hypoxia, an attenuated hyperventilatory response was observed. In this test, there were also indications that prior ethanol exposure depressed breathing frequencies during hypoxia and a recovery normoxia phase. Conclusion: As a whole, the results demonstrated that brief ethanol experience and stress-related factors significantly disorganize respiratory patterns as well as arousal responses linked to hypoxia in neonatal rats.Fil: Macchione, Ana Fabiola. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; ArgentinaFil: Anunziata, Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; ArgentinaFil: Haymal, Olga Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; ArgentinaFil: Abate, Paula. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; ArgentinaFil: Molina, Juan Carlos. University of Binghamton; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; Argentin

Co-existence of ethanol-related respiratory and motivational learning processes based on a tactile discrimination procedure in neonatal rats

In rats, high ethanol doses during early postnatal life exert deleterious effects upon brain development that impact diverse social and cognitive abilities. This stage in development partially overlaps with the third human gestational trimester, commonly referred to as the brain growth spurt period. At this stage in development, human fetuses and rat neonates (postnatal days [PD] 3–9) exhibit relatively high respiratory rates that are affected by subteratogenic ethanol doses. Recent studies suggest conditioned breathing responses in the developing organism, given that there are explicit associations between exteroceptive stimuli and the state of ethanol intoxication. Furthermore, studies performed with near-term rat fetuses suggest heightened sensitivity to ethanol's motivational effects. The present study was meant to analyze the unconditioned effects of ethanol intoxication and the possible co-occurrence of learning mechanisms that can impact respiratory plasticity, and to analyze the preference for cues that signal the state of intoxication as well as the effects of the drug, related with motor stimulation. Neonatal rats were subjected to differential experiences with salient tactile cues explicitly paired or not paired with the effects of vehicle or ethanol (2.0 g/kg). A tactile discrimination procedure applied during PDs 3, 5, 7, and 9 allowed the identification of the emergence of ethanol-derived non-associative and associative learning processes that affect breathing plasticity, particularly when considering apneic disruptions. Ethanol was found to partially inhibit the disruptions that appeared to be intimately related with stressful circumstances defined by the experimental procedure. Tactile cues paired with the drug's effects were also observed to exert an inhibitory effect upon these breathing disruptions. The level of contingency between a given tactile cue and ethanol intoxication also resulted in significant changes in the probability of seeking this cue in a tactile preference test. In addition, the state of intoxication exerted motor-stimulating effects. When contrasting the data obtained via the analysis of the different dependent variables, it appears that most ethanol-derived changes are modulated by positive and/or negative (anti-anxiety) reinforcing effects of the drug. As a whole, the study indicates co-existence of ethanol-related functional changes in the developing organism that simultaneously affect respiratory plasticity and preference patterns elicited by stimuli that signal ethanol's motivational effects. These results emphasize the need to consider significant alterations due to minimal ethanol experiences that argue against “safe” levels of exposure in a critical stage in brain development.Fil: D'aloisio, Génesis. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; ArgentinaFil: Acevedo, María Belén. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; ArgentinaFil: Macchione, Ana Fabiola. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; ArgentinaFil: Anunziata, Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; ArgentinaFil: Molina, Juan Carlos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; Argentin

Neonatal experiences with ethanol intoxication modify respiratory and thermoregulatory plasticity and affect subsequent ethanol intake in rats

Different studies have focused on the deleterious consequences of binge-like or chronic exposure to ethanol during the brain growth spurt period (third human gestational trimester) that in the rat corresponds to postnatal days (PDs) 3–10. The present study analyzed behavioral and physiological disruptions caused by relatively brief binge-like exposures (PDs 3, 5, and 7) with an ethanol dose lower (3.0 g/kg) than those frequently employed to examine teratological effects during this stage in development. At PD 9, pups were exposed to ethanol doses ranging between.0–3.0 g/kg and tested in terms of breathing patterns and thermoregulation. At PDs 11 and 12, ethanol intake was examined. The main findings were as follows: i) pre-exposure to the drug resulted in brief depressions in breathing frequencies and an exacerbated predisposition toward apneic episodes; ii) these effects were not dependent upon thermoregulatory alterations; iii) early ethanol treatment increased initial consumption of the drug which also caused a marked hypothermia that appeared to regulate a subsequent decrement in ethanol consumption; and iv) ethanol exposure retarded overall body growth and even one exposure to the drug (PD 9) was sufficient to reduce brain weights although there were no indications of microcephaly. In conjunction with studies performed during the late gestational period in the rat, the results indicate that relatively brief binge-like episodes during a critical window of brain vulnerability disrupts the respiratory network and exacerbates initial acceptance of the drug. In addition, ethanol treatments were not found to induce tolerance relative to respiratory and thermal disruptions.Fil: Acevedo, María Belén. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; ArgentinaFil: Macchione, Ana Fabiola. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; ArgentinaFil: Anunziata, Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; ArgentinaFil: Haymal, Olga Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; ArgentinaFil: Molina, Juan Carlos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; Argentin