Estrogen blocks the protective action of melatonin in a behavioral model of ethanol-induced hangover in mice

Melatonin has antioxidant and neuroprotective properties in human beings and experimental models, as well as 'anti-estrogenic' effects. Ethanol (EtOH) affects various behavioral parameters during a period known as ethanol-induced hangover. Our study evaluated the neuroprotective effect of melatonin on motor performance during ethanol hangover in male and female Swiss mice. The females were subjected to specific hormonal states: ovariectomized (OVX) and OVX estrogenized (OVX-E2). Mice received melatonin (25μg/ml) or vehicle in their drinking water for seven days and were given intraperitoneal (i.p.) injections of EtOH (3.8g/kg) or saline on the morning of the eighth day. Motor performance was evaluated by the tightrope test 6h after EtOH exposure (hangover onset). During ethanol hangover, males exhibited lower motor performance than controls (p<0.01) but pretreatment with melatonin significantly improved performance during hangover (p<0.05). In females, melatonin treatment before ethanol-induced hangover led to a better motor performance in OVX compared with intact females (p<0.01) and a lower performance in OVX-E2 compared with not-estrogenized OVX (p<0.05). Consequently, estrogen reversed the motor performance enhancement afforded by melatonin. We conclude that estrogen interferes with the protective action of melatonin on motor performance during ethanol hangover.Fil: Karadayian, A. G.. Universidad de Buenos Aires. Facultad de Medicina; ArgentinaFil: Mc Laughlin, M. A.. Universidad de Buenos Aires. Facultad de Medicina; ArgentinaFil: Cutrera, Rodolfo Angel. Universidad de Buenos Aires. Facultad de Medicina; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentin

Alterations of motor performance and brain cortex mitochondrial function during ethanol hangover

Ethanol has been known to affect various behavioral parameters in experimental animals, even several hours after ethanol (EtOH) is absent from blood circulation, in the period known as hangover. The aim of this study was to assess the effects of acute ethanol hangover on motor performance in association with the brain cortex energetic metabolism. Evaluation of motor performance and brain cortex mitochondrial function during alcohol hangover was performed in mice 6 hours after a high ethanol dose (hangover onset). Animals were injected i.p. either with saline (control group) or with ethanol (3.8 g/kg BW) (hangover group). Ethanol hangover group showed a bad motor performance compared with control animals (p < .05). Oxygen uptake in brain cortex mitochondria from hangover animals showed a 34% decrease in the respiratory control rate as compared with the control group. Mitochondrial complex activities were decreased being the complex I-III the less affected by the hangover condition; complex II-III was markedly decreased by ethanol hangover showing 50% less activity than controls. Complex IVwas 42% decreased as compared with control animals. Hydrogen peroxide production was 51% increased in brain cortex mitochondria from the hangover group, as compared with the control animals. Quantification of the mitochondrial transmembrane potential indicated that ethanol injected animals presented 17% less ability to maintain the polarized condition as compared with controls. These results indicate that a clear decrease in proton motive force occurs in brain cortex mitochondria during hangover conditions. We can conclude that a decreased motor performance observed in the hangover group of animals could be associated with brain cortex mitochondrial dysfunction and the resulting impairment of its energetic metabolism.Fil: Bustamante, Juanita. Universidad de Buenos Aires; ArgentinaFil: Karadayian, Analia Graciela. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Ciencias Fisiológicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; ArgentinaFil: Lores Arnaiz, Silvia. Universidad de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; ArgentinaFil: Cutrera, Rodolfo Angel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Ciencias Fisiológicas; Argentin

Different effects by sex on hypothalamic-pituitary axis of prepubertal offspring rats produced by in utero and lactational exposure to di-(2-ethylhexyl) phthalate (DEHP)

This study investigated the effect of pre and perinatal exposure to di-(2-ethylhexyl) phthalate (DEHP) on the neuroendocrine parameters that regulate reproduction in prepubertal male and female rats. DEHP at doses of 3 and 30 mg/kg. bw/day was administered orally in the drinking water to dam rats since pregnancy onset until the moment of pups sacrifice at 15 days of age. In these animals gonadotropin serum level and the hypothalamic contents of the amino acids aspartate, glutamate and gamma-aminobutyric acid were determined. No changes in gonadotropin levels and amino acid neurotransmitters were detected at the low dose in both sexes. However, DEHP administered at high dose (30 mg/kg bw/day) to dams produced a significant decrease in the inhibitory neurotransmitter GABA and an increase in the stimulatory neurotransmitter aspartate in prepubertal male offspring rats. These modifications were accompanied by gonadotropin serum levels increase. On the contrary, in treated female rats this chemical increased both, aspartate and GABA, which exert a characteristic stimulatory action on gonadotropin in 15-day-old normal females. This study provides new data about changes produced by DEHP on the hypothalamic amino acid neurotransmitters involved in the neuroendocrine reproductive regulation, in prepubertal male and female rat offspring from dams exposed during gestational and lactational periods. These alterations induced by DEHP exposure could be related to the gonadotropin modifications also described in this work, and with changes in the production of sexual hormones previously reported by other authors.Fil: Carbone, Silvia Elena. Universidad Favaloro; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina; ArgentinaFil: Samaniego, Yanina A.. Universidad de Buenos Aires. Facultad de Medicina; ArgentinaFil: Cutrera, Rodolfo Angel. Universidad de Buenos Aires. Facultad de Medicina; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Reynoso, R.. Universidad de Buenos Aires. Facultad de Medicina; ArgentinaFil: Cardoso, N.. Universidad de Buenos Aires. Facultad de Medicina; ArgentinaFil: Scacchi, Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina; Argentina. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires"; ArgentinaFil: Moguilevsky, Jaime Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Favaloro; ArgentinaFil: Ponzo, Osvaldo Juan. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina; Argentin

Alcohol hangover: type and time-extension of motor function impairments

Alcohol hangover is defined as the unpleasant next-day state following an evening of excessive alcohol consumption. Hangover begins when ethanol is absent in plasma and is characterized by physical and psychological symptoms. During hangover cognitive functions and subjective capacities are affected along with inefficiency, reduced productivity, absenteeism, driving impairments, poor academic achievement and reductions in motor coordination. The aim of this work was to study the type and length of motor and exploratory functions from the beginning to the end of the alcohol hangover. Male Swiss mice were injected i.p. either with saline (control group) or with ethanol (3.8 g/kg BW) (hangover group). Motor performance, walking deficiency, motor strength, locomotion and exploratory activity were evaluated at a basal point (ZT0) and every 2 h up to 20 h after blood alcohol levels were close to zero (hangover onset). Motor performance was 80% decreased at the onset of hangover (p < 0.001). Hangover mice exhibited a reduced motor performance during the next 16 h (p < 0.01). Motor function was recovered 20 h after hangover onset. Hangover mice displayed walking deficiencies from the beginning to 16 h after hangover onset (p < 0.05). Moreover, mice suffering from a hangover, exhibited a significant decrease in neuromuscular strength during 16 h (p < 0.001). Averaged speed and total distance traveled in the open field test and the exploratory activity on T-maze and hole board tests were reduced during 16 h after hangover onset (p < 0.05). Our findings demonstrate a time-extension between 16 to 20 h for hangover motor and exploratory impairments. As a whole, this study shows the long lasting effects of alcohol hangover.Fil: Karadayian, Analia Graciela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Bioquímica y Medicina Molecular; Argentina. Universidad Favaloro. Facultad de Medicina. Departamento de Cs.fisiologicas; ArgentinaFil: Cutrera, Rodolfo Angel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Ciencias Fisiológicas; Argentin

Effect of N-Methyl-D-Aspartate Receptor Blockade on Anxiety-Like Behavior Induced in Rats by Postnatal Chronic Exposure to the Endocrine Disruptor Di-2 (Ethyl-Hexyl Phthalate) in Elevated plus Maze Test

Di-2-Ethylhexyl Phthalate (DEHP) is the widely used to convey flexibility and transparency to plastic products made of polyvinyl chloride and also in the manufacture of medical devices. DEHP disrupts reproductive tract development in an antiandrogenic manner and also may induce neurobehavioral changes. In previous works, we demonstrated that chronic postnatal exposure to DEHP alters the neuroendocrine regulation of the testicular axis, modifying the hypothalamic concentration of excitatory neurotransmitters and therefore induces an anxiogenic effect. In the Elevated Plus Maze (EPM) test, dizocilpine (MK-801) induces a decrease in anxiety-related behaviors throughout NMDA receptor blockade. The objective of this work was to investigate whether the blockade of NMDA receptors of glutamate by the non-competitive antagonist MK-801 could modify the anxiety-like behavior induced by chronic postnatal exposure to DEHP (30 mg/kg body weight/day, orally from birth) in young adult male rats in the EPM test. The results show that NMDA receptor blockade by MK-801 (0.1 mg/kg body weight, i.p.) in DEHP exposed animals is able to produce a significant decrease in time spent in closed arms (TSC) and in Freezing Time (FT) as well as an increase in time spent in open arms (TSO) in the EPM test, indicating an anxiolytic effect. In conclusion, our results suggest: 1) NMDA receptor blockade by MK-801 can reverse anxiety-like behavior induced by exposure to DEHP during the early period of life. 2) The glutamatergic system is involved in the anxiogenic effect of phthalate, which is probably triggered by its known antiandrogenic action.Fil: Carbone, Silvia Elena. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; ArgentinaFil: Ponzo, Osvaldo Juan. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Ciencias Fisiológicas; ArgentinaFil: Cutrera, Rodolfo Angel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; Argentin

The effect of constant darkness and circadian resynchronization on the recovery of alcohol hangover

Alcohol hangover (AH) is a particular state after binge-like drinking. AH begins when ethanol is absent in plasma and is characterized by a cluster of physical and psychological symptoms. Alcohol disrupts circadian patterns of behavioral and physiological parameters; however, the involvement of circadian clock on the recovery of AH was not explored. Our aim was to study the effect of continuous darkness and the possible involvement of the circadian clock in the recovery time of neuromuscular impairment and anxiety related-behavior due to AH. Male Swiss mice were habituated to 12:12 L:D or continuous darkness. Each group was injected i.p. either with saline (control group) or with ethanol (3.8 g/kg BW) (hangover group). Motor performance and anxiety phenotype were evaluated at a basal point (ZT0) and every 2 h up to 20 h after blood alcohol levels were close to zero (hangover onset). A third group was subjected to a phase advance during which a hangover episode was induced and behavioral tests were carried out for each group of treatment and resynchronization day. Constant darkness resulted to be in a faster recovery of both motor and anxiety impairments in AH compared with the recovery pattern observed under normal light–dark conditions. Mice suffering from a phase shift exhibited behavioral disruptions due to both AH and phase advance. Results indicated that a synchronized circadian clock is necessary for an adequate recovery of alcohol hangover symptoms.Fil: Karadayian, Analia Graciela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Bioquímica y Medicina Molecular; Argentina. Universidad de Buenos Aires. Facultad de Medicina; ArgentinaFil: Lores Arnaiz, Silvia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Bioquímica y Medicina Molecular; ArgentinaFil: Cutrera, Rodolfo Angel. Universidad de Buenos Aires. Facultad de Medicina; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Autonomic neural signals in bone: Physiological implications for mandible and dental growth

Signals derived from the autonomic nervous system exert potent effects on osteoclast and osteoblast function. A ubiquitous sympathetic and sensory innervation of all periosteal surfaces exists and its disruption affects bone remodeling. Several neuropeptides, neurohormones and neurotransmitters and their receptors are detectable in bone. Bone mineral content decreased in sympathetically denervated mandibular bone. When a mechanical stress was superimposed on mandibular bone by cutting out the lower incisors, an increase in bone density ensued providing the sympathetic innervation was intact. A lower eruption rate of sympathetically denervated incisors at the impeded eruption side, and a higher eruption rate of denervated incisors at the unimpeded side were also observed. A normal sympathetic neural activity appears to be a pre-requisite for maintaining a minimal normal unimpeded incisor eruption and for keeping the unimpeded eruption to attain abnormally high velocities under conditions of stimulated incisor growth. These and other results suggest that the sympathetic nervous system plays an important role in mandibular bone metabolism.Fil: Boggio, Veronica Ines. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina; ArgentinaFil: Ladizesky, Marta Graciela. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Cutrera, Rodolfo Angel. Universidad de Buenos Aires. Facultad de Medicina; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Cardinali, Daniel Pedro. Universidad de Buenos Aires. Facultad de Medicina; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Behavioral effects of the combined use of alcohol and energy drinks on alcohol hangover in an experimental mice model

In last few years it has been a significant increase in the consumption of alcohol combined with energy drink. The aim of this work was to study the effect of this mixture in motor and affective behaviors during an alcohol hangover episode. Male Swiss mice received one of the following treatments: saline + sucrose; saline + energy drink; ethanol + sucrose; ethanol + energy drink. Ethanol dose was 3.8 g/kg BW (i.p.) and energy drink dose was 18 ml/kg BW (gavage) at ZT1 (8 am) (ZT: Zeitgeber time; ZT0: 7 am; lights on). The behavioral tests used were tight rope test to determine motor coordination; hanging wire test to study muscular strength; elevated plus maze and open field tests to evaluate anxiety like-behavior and locomotor activity. Tests were carried out at basal point that matched with lights onset and every 6 h up to 18 h after treatments. Hangover onset was established at ZT7 when blood alcohol concentration (BAC) was almost zero. Our results showed that the mixture of alcohol and energy drink altered significantly motor skills. Specifically, a significant decrease was observed in the performance of the animals in the tightrope and hanging wire tests in groups treated with the mixture of alcohol and energy drink. A significant impairment in the anxiety-like behavior was observed mainly at the beginning of alcohol hangover. These findings suggest that energy drink added to alcohol extends motor disabilities observed during an alcohol hangover episode in comparison with animals that received alcohol alone.Fil: Asorey, Lucas Gustavo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; ArgentinaFil: Carbone, Silvia Elena. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Ciencias Fisiológicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; ArgentinaFil: Gonzalez, Bárbara J.. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Ciencias Fisiológicas; ArgentinaFil: Cutrera, Rodolfo Angel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; Argentin

Changes in motor function and brain cortex mitochondrial active oxygen species production in aged mice

Neuronal ageing is a complex physiological process, associated to metabolic and motor changes. In this study, 3 and 17 months old male Swiss mice were used. Aged mice exhibited a significant reduction in motor performance and walking footprint pattern. Synaptosomes and mitochondrial fractions were isolated from mouse brain cortex. Active oxygen species and cardiolipin content were measured in both subcellular fractions. Synaptosomal acetylcholinesterase activity was measured in both animal age groups. Results showed that superoxide levels were 42.9% lower in synaptosomes from old mice as compared with young animals, while no changes were observed in non-synaptic mitochondria. Succinate-glutamate dependent H 2 O 2 production rate was 27.5% decreased in non-synaptic mitochondria from aged mice. Cardiolipin content was 21% decreased in synaptosomes from 17-months old animals, while no changes were observed in non-synaptic mitochondria. Acetylcholinesterase activity decreased 16% in 17-months old mice, as compared with young animals. Age-related alterations in neuronal function could be associated with changes in active oxygen species at synapses, with parallel motor deficiencies.Fil: Lores Arnaiz, Silvia. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; ArgentinaFil: Lombardi, P.. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; ArgentinaFil: Karadayian, Analia Graciela. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; ArgentinaFil: Cutrera, Rodolfo Angel. Universidad de Buenos Aires. Facultad de Medicina; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; ArgentinaFil: Bustamante, J.. Universidad Abierta Interamericana; Argentin

Alterations in affective behavior during the time course of alcohol hangover

Alcohol hangover is a temporary state described as the unpleasant next-day effects after binge-like drinking. Hangover begins when ethanol is absent in plasma and is characterized by physical and psychological symptoms. Affective behavior is impaired during the acute phase of alcohol intoxication; however, no reports indicate if similar effects are observed during withdrawal. The aim of this work was to study the time-extension and possible fluctuations in affective behavior during a hangover episode. Male Swiss mice were injected i.p. either with saline (control group) or with ethanol (3.8. g/kg BW) (hangover group). Anxiety, fear-related behavior and despair phenotype were evaluated at a basal point (ZT0) and every 2. h up to 20. h after blood alcohol levels were close to zero (hangover onset). Also, anhedonia signs and pain perception disabilities were studied. Mice exhibited an increase in anxiety-like behavior during 4. h and 14. h after hangover onset when evaluated by the elevated-plus maze and open field test respectively (p<. 0.05). Fear-related behavior was detected in hangover animals by the increase of freezing and decrease of line crossings and rearing frequency during 16. h after hangover onset (p<. 0.001). Depression signs were found in hangover mice during 14. h (p<. 0.05). Hangover mice showed a significant decrease in pain perception when tested by tail immersion test at the beginning of hangover (p<. 0.05). Our findings demonstrate a time-extension between 14 and 16. h for hangover affective impairments. This study shows the long lasting effects of hangover over the phase of ethanol intoxication. © 2013 Elsevier B.V.Fil: Karadayian, Analia Graciela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Bioquímica y Medicina Molecular. Universidad de Buenos Aires. Facultad Medicina. Instituto de Bioquímica y Medicina Molecular; ArgentinaFil: Busso, María Julia. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Ciencias Fisiológicas; ArgentinaFil: Feleder, Carlos Alberto. The Albany Medical College; Estados UnidosFil: Cutrera, Rodolfo Angel. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Ciencias Fisiológicas; Argentin