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1.
Genes Brain Behav ; 12(7): 714-22, 2013 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-23876074

RESUMEN

Using chromosome substitution strains (CSS), we previously identified a large quantitative trait locus (QTL) for conditioned fear (CF) on mouse chromosome 10. Here, we used an F2 cross between CSS-10 and C57BL/6J (B6) to localize that QTL to distal chromosome 10. That QTL accounted for all the difference between CSS-10 and B6. We then produced congenic strains to fine-map that interval. We identified two congenic strains that captured some or all the QTL. The larger congenic strain (Line 1: 122.387121-129.068 Mb; build 37) appeared to account for all the difference between CSS-10 and B6. The smaller congenic strain (Line 2: 127.277-129.068 Mb) was intermediate between CSS-10 and B6. We used haplotype mapping followed by quantitative polymerase chain reaction to identify one gene that was differentially expressed in both lines relative to B6 (Rnf41) and one that was differentially expressed between only Line 1 and B6 (Shmt2). These cis-eQTLs may cause the behavioral QTLs; however, further studies are required to validate these candidate genes. More generally, our observation that a large QTL mapped using CSS and F2 crosses can be dissected into multiple smaller QTLs shows a weaknesses of two-stage approaches that seek to use coarse mapping to identify large regions followed by fine-mapping. Indeed, additional dissection of these congenic strains might result in further subdivision of these QTL regions. Despite these limitations, we have successfully fine-mapped two QTLs to small regions and identified putative candidate genes, showing that the congenic approach can be effective for fine-mapping QTLs.


Asunto(s)
Ansiedad/genética , Cromosomas de los Mamíferos/genética , Miedo , Sitios de Carácter Cuantitativo , Animales , Ansiedad/fisiopatología , Proteínas Portadoras/genética , Mapeo Cromosómico , Cruzamientos Genéticos , Haplotipos , Ratones , Ratones Endogámicos C57BL , Ubiquitina-Proteína Ligasas
2.
Genes Brain Behav ; 11(5): 623-32, 2012 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-22487465

RESUMEN

We previously used the C57BL/6J (B6) × A/J mouse chromosome substitution strain (CSS) panel to identify a major quantitative trait locus (QTL) on chromosome 11 influencing methamphetamine (MA)-induced locomotor activity. We then made an F(2) cross between CSS-11 and B6 and narrowed the locus (Bayes credible interval: 79-109 Mb) which was inherited dominantly and accounted for 14% of the phenotypic variance in the CSS panel. In the present study, we created congenic and subcongenic lines possessing heterozygous portions of this QTL to narrow the interval. We identified one line (84-96 Mb) that recapitulated the QTL, thus narrowing the region to 12 Mb. This interval also produced a small decrease in locomotor activity following prior saline treatment. When we generated subcongenic lines spanning the entire 12-Mb region, the phenotypic difference in MA sensitivity abruptly disappeared, suggesting an epistatic mechanism. We also evaluated the rewarding properties of MA (2 mg/kg, i.p.) in the 84- to 96-Mb congenic line using the conditioned place preference (CPP) test. We replicated the locomotor difference in the MA-paired CPP chamber yet observed no effect of genotype on MA-CPP, supporting the specificity of this QTL for MA-induced locomotor activity under these conditions. Lastly, to aid in prioritizing candidate genes responsible for this QTL, we used the Affymetrix GeneChip(®) Mouse Gene 1.0ST Array to identify genes containing expression QTLs (eQTL) in the striatum of drug-naÏve, congenic mice. These findings highlight the difficulty of using congenic lines to fine map QTLs and illustrate how epistasis may thwart such efforts.


Asunto(s)
Estimulantes del Sistema Nervioso Central/farmacología , Epistasis Genética , Interacción Gen-Ambiente , Metanfetamina/farmacología , Actividad Motora/efectos de los fármacos , Actividad Motora/genética , Sitios de Carácter Cuantitativo , Animales , Mapeo Cromosómico , Predisposición Genética a la Enfermedad , Genotipo , Ratones , Ratones Congénicos
3.
Genes Brain Behav ; 11(1): 52-61, 2012 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-22032291

RESUMEN

Sensitivity to the locomotor stimulant effects of methamphetamine (MA) is a heritable trait that utilizes neurocircuitry also associated with the rewarding effects of drugs. We used the power of a C57BL/6J × DBA/2J F(2) intercross (n = 676) and the precision of a C57BL/6J × DBA/2J F(8) advanced intercross line (Aap: B6, D2-G8; or F(8) AIL; n = 552) to identify and narrow quantitative trait loci (QTLs) associated with sensitivity to the locomotor stimulant effects of MA. We used the program QTLRel to simultaneously map QTL in the F(2) and F(8) AIL mice. We identified six genome-wide significant QTLs associated with locomotor activity at baseline and seven genome-wide significant QTLs associated with MA-induced locomotor activation. The average per cent decrease in QTL width between the F(2) and the integrated analysis was 65%. Additionally, these QTLs showed a distinct temporal specificity within each session that allowed us to further refine their locations, and identify one QTL with a 1.8-LOD support interval of 1.47 Mb. Next, we utilized publicly available bioinformatics resources to exploit strain-specific sequence data and strain- and region-specific expression data to identify candidate genes. These results illustrate the power of AILs in conjunction with sequence and gene expression data to investigate the genetic underpinnings of behavioral and other traits.


Asunto(s)
Conducta Animal/efectos de los fármacos , Mapeo Cromosómico , Regulación de la Expresión Génica/genética , Metanfetamina/farmacología , Actividad Motora/efectos de los fármacos , Sitios de Carácter Cuantitativo/genética , Animales , Estimulantes del Sistema Nervioso Central/farmacología , Biología Computacional , Cruzamientos Genéticos , Bases de Datos Genéticas , Femenino , Regulación de la Expresión Génica/efectos de los fármacos , Genética Conductual , Estudio de Asociación del Genoma Completo , Endogamia , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Endogámicos DBA , Actividad Motora/genética , Recompensa
4.
Genes Brain Behav ; 10(5): 604-14, 2011 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-21554534

RESUMEN

Anxiety, like other psychiatric disorders, is a complex neurobehavioral trait, making identification of causal genes difficult. In this study, we examined anxiety-like behavior and fear conditioning (FC) in an F(2) intercross of C57BL/6J and DBA/2J mice. We identified numerous quantitative trait loci (QTL) influencing anxiety-like behavior in both open field (OF) and FC tests. Many of these QTL were mapped back to the same chromosomal regions, regardless of behavior or test. For example, highly significant overlapping QTL on chromosome 1 were found in all FC measures as well as in center time measures in the OF. Other QTL exhibited strong temporal profiles over testing, highlighting dynamic relationship between genotype, test and changes in behavior. Next, we implemented a factor analysis design to account for the correlated nature of the behaviors measured. OF and FC behaviors loaded onto four main factors representing both anxiety and fear behaviors. Using multiple QTL modeling, we calculated the percentage variance in anxiety and fear explained by multiple QTL using both additive and interactive terms. Quantitative trait loci modeling resulted in a broad description of the genetic architecture underlying anxiety and fear accounting for 14-37% of trait variance. Factor analysis and multiple QTL modeling showed both unique and shared QTL for anxiety and fear; suggesting a partially overlapping genetic architecture for these two different models of anxiety.


Asunto(s)
Ansiedad/genética , Conducta Animal/fisiología , Miedo/fisiología , Sitios de Carácter Cuantitativo , Animales , Condicionamiento Psicológico/fisiología , Cruzamientos Genéticos , Femenino , Genotipo , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Endogámicos DBA , Actividad Motora/genética , Fenotipo
5.
Genes Brain Behav ; 9(7): 759-67, 2010 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-20597988

RESUMEN

Prepulse inhibition (PPI) of the startle response is a measure of sensorimotor gating, a process that filters out extraneous sensory, motor and cognitive information. Humans with neurological and psychiatric disorders, including schizophrenia, obsessive-compulsive disorder and Huntington's disease, exhibit a reduction in PPI. Habituation of the startle response is also disrupted in schizophrenic patients. In order to elucidate the genes involved in sensorimotor gating, we phenotyped 472 mice from an F(2) cross between LG/J × SM/J for PPI and genotyped these mice genome-wide using 162 single nucleotide polymorphism (SNP) markers. We used prepulse intensity levels that were 3, 6 and 12 dB above background (PPI3, PPI6 and PPI12, respectively). We identified a significant quantitative trait locus (QTL) on chromosome 12 for all three prepulse intensities as well as a significant QTL for both PPI6 and PPI12 on chromosome 11. We identified QTLs on chromosomes 7 and 17 for the startle response when sex was included as an interactive covariate and found a QTL for habituation of the startle response on chromosome 4. We also phenotyped 135 mice from an F(34) advanced intercross line (AIL) between LG/J × SM/J for PPI and genotyped them at more than 3000 SNP markers. Inclusions of data from the AIL mice reduced the size of several of these QTLs to less than 5 cM. These results will be useful for identifying genes that influence sensorimotor gaiting and show the power of AIL for fine mapping of QTLs.


Asunto(s)
Sitios de Carácter Cuantitativo/genética , Reflejo de Sobresalto/genética , Reflejo de Sobresalto/fisiología , Filtrado Sensorial/genética , Filtrado Sensorial/fisiología , Estimulación Acústica , Análisis de Varianza , Animales , Mapeo Cromosómico , Cruzamientos Genéticos , Femenino , Marcadores Genéticos , Genotipo , Habituación Psicofisiológica/genética , Escala de Lod , Masculino , Ratones , Ratones Endogámicos , Polimorfismo de Nucleótido Simple , Análisis de Componente Principal , Caracteres Sexuales , Especificidad de la Especie
6.
Dev Psychobiol ; 39(2): 65-75, 2001 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-11568876

RESUMEN

Huddling is expressed by infant rats and continues to be an important behavior throughout adulthood. As a form of behavioral thermoregulation, huddling is thought to play an essential role in compensating for inadequate physiological thermoregulation early in development. Infant rats, however, are capable of heat production shortly after birth using brown adipose tissue (BAT) and exhibit thermogenesis in the huddle, suggesting that huddling does not obviate the need for endothermy during cold exposure. In the present experiment, 4-pup huddles of infant rats (2- or 8-day-olds) were exposed to two subthermoneutral temperatures, and BAT thermogenesis was inhibited in 0, 2, or 4 of the rats in each huddle. Inhibition of BAT thermogenesis compromised the pups' ability to maintain huddle temperature, but surprisingly did not result in enhanced huddling at either age. These results suggest that effective huddling during cold exposure requires the thermal resources provided by endothermy. Furthermore, the heat provided by BAT appears to shape behavioral interactions in the huddle during development.


Asunto(s)
Conducta Animal/fisiología , Conducta Competitiva , Conducta Cooperativa , Animales , Animales Recién Nacidos , Temperatura Corporal/fisiología , Regulación de la Temperatura Corporal/fisiología , Ratas , Ratas Sprague-Dawley
7.
Psychol Rev ; 108(1): 83-95, 2001 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-11212634

RESUMEN

In the current revival of interest in the emotional and mental lives of animals, many investigators have focused attention on mammalian infants that emit distress vocalizations when separated from the home environment. Perhaps the most intensively studied distress vocalization is the ultrasonic vocalization of infant rats. Since its discovery, this vocalization has been interpreted both as a communicatory signal for the elicitation of maternal retrieval and as the manifestation of emotional distress. In contrast, the authors examined the cardiovascular causes and consequences of the vocalization, and on the basis of this work, they hypothesized that the vocalization is the acoustic by-product of the abdominal compression reaction (ACR), a maneuver that results in increased venous return to the heart. Therefore, the vocalization may be analogous to a sneeze, serving a physiological function while incidentally producing sound.


Asunto(s)
Fenómenos Fisiológicos Cardiovasculares , Llanto , Estrés Psicológico , Vocalización Animal , Agonistas alfa-Adrenérgicos/farmacología , Animales , Clonidina/farmacología , Llanto/fisiología , Llanto/psicología , Ratas , Ultrasonido , Vocalización Animal/efectos de los fármacos , Vocalización Animal/fisiología
8.
Behav Neurosci ; 114(3): 585-93, 2000 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-10883808

RESUMEN

In infant rats, huddling improves surface-to-volume ratios and provides metabolic savings during cold exposure. It is unclear, however, whether endothermy is also a necessary component of huddling. In the present experiment, huddles composed of infant Norway rats (2- or 8-day-olds), which produce heat endogenously, or Syrian golden hamsters (8-day-olds), which do not produce heat endogenously, were exposed to decreases in air temperature. Behavioral and physiological responses were monitored throughout the test. Rats, especially at 8 days of age, were better able to thermoregulate using huddling than hamsters, due in part to endogenous heat production. Furthermore, 8-day-old rats exhibited behavioral responses that promote heat retention, suggesting that both physiological and behavioral mechanisms contribute to effective thermoregulation during huddling in the cold.


Asunto(s)
Animales Recién Nacidos/fisiología , Regulación de la Temperatura Corporal/fisiología , Medio Social , Tejido Adiposo Pardo/fisiología , Animales , Cricetinae , Metabolismo Energético/fisiología , Mesocricetus , Consumo de Oxígeno/fisiología , Ratas , Vocalización Animal/fisiología
9.
Behav Neurosci ; 114(3): 602-8, 2000 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-10883810

RESUMEN

In infant rats, administration of the alpha2 adrenoceptor agonist clonidine simultaneously evokes ultrasound production and bradycardia. In this study the authors examined in 8-day-old rats whether these 2 responses to clonidine are causally related. In Experiment 1 pups were pretreated with saline or prenalterol (0.1 or 1.0 mg/kg), a beta1 adrenoceptor agonist that increases cardiac rate, followed by administration of clonidine (1.0 mg/kg). Prenalterol pretreatment suppressed clonidine-induced ultrasound production at both doses. Prenalterol also increased skin temperature, however, suggesting that suppression of ultrasound was modulated in part by increased body temperature. Consistent with this suggestion, in Experiment 2 mild hyperthermia significantly inhibited clonidine-induced ultrasound production. Finally, in Experiment 3 the authors found that the pretreatments used in Experiments 1 and 2 prevent or dampen the effects of clonidine on cardiac rate. These results suggest that clonidine's effect on ultrasound production is mediated by its effects on the cardiovascular system.


Asunto(s)
Agonistas alfa-Adrenérgicos/farmacología , Clonidina/farmacología , Frecuencia Cardíaca/efectos de los fármacos , Vocalización Animal/efectos de los fármacos , Agonistas Adrenérgicos beta/farmacología , Animales , Nivel de Alerta/efectos de los fármacos , Regulación de la Temperatura Corporal/efectos de los fármacos , Sistema Cardiovascular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Femenino , Masculino , Premedicación , Prenalterol/farmacología , Ratas , Ratas Sprague-Dawley
10.
Dev Psychobiol ; 36(3): 186-93, 2000 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-10737864

RESUMEN

Under controlled conditions, infant rats emit ultrasonic vocalizations during extreme cold exposure and after administration of the alpha(2) adrenoceptor agonist, clonidine. Previous investigations have determined that, in response to clonidine, ultrasound production increases through the 2nd-week postpartum and decreases thereafter. Given that sympathetic neural dominance exhibits a similar developmental pattern, and given that clonidine induces sympathetic withdrawal and bradycardia, we hypothesized that clonidine's developmental effects on cardiac rate and ultrasound production would mirror each other. Therefore, in the present experiment, the effects of clonidine administration (0.5 mg/kg) on cardiac rate and ultrasound production were examined in 2-, 8-, 15-, and 20-day-old rats. Age-related changes in ultrasound production corresponded with changes in cardiovascular variables, including baseline cardiac rate and clonidine-induced bradycardia. This experiment is discussed with regard to the hypothesis that ultrasound production is the acoustic by-product of a physiological maneuver that compensates for clonidine's detrimental effects on cardiovascular function.


Asunto(s)
Clonidina/farmacología , Frecuencia Cardíaca/efectos de los fármacos , Ratas Sprague-Dawley/crecimiento & desarrollo , Simpaticolíticos/farmacología , Vocalización Animal/efectos de los fármacos , Animales , Sistema Nervioso Autónomo/efectos de los fármacos , Sistema Nervioso Autónomo/crecimiento & desarrollo , Conducta Animal/efectos de los fármacos , Bradicardia/inducido químicamente , Clonidina/administración & dosificación , Femenino , Masculino , Ratas , Simpaticolíticos/administración & dosificación
11.
Psychol Sci ; 11(1): 78-81, 2000 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-11228849

RESUMEN

Ultrasonic vocalizations emitted by infant rodents are typically characterized as cries of distress. There are two contexts that are known to reliably elicit ultrasound production: extreme cold exposure and administration of clonidine, an alpha 2 adrenoceptor agonist. Noting that these two contexts both entail pronounced decreases in cardiac rate, we have hypothesized that the vocalizations are acoustic by-products of a physiological maneuver, the abdominal compression reaction (ACR), that increases venous return to the heart when return is compromised. As a critical test of this hypothesis, we measured venous pressure near the right atrium in 15-day-old rats after clonidine administration. Consistent with the ACR hypothesis, emission of ultrasound was accompanied by large and reliable increases in venous pressure and, therefore, venous return. These results provide strong, direct support for the ACR hypothesis and, by doing so, underscore the potential pitfalls of anthropomorphic interpretations of the vocalizations of infant rats.


Asunto(s)
Función Atrial , Vocalización Animal , Abdomen , Animales , Animales Recién Nacidos/psicología , Presión Sanguínea , Femenino , Hemodinámica , Masculino , Ratas , Ratas Sprague-Dawley , Ultrasonido
12.
Hypertension ; 33(6): 1465-9, 1999 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-10373234

RESUMEN

Cardiovascular function during cold exposure is dependent on effective thermoregulation. This dependence is particularly apparent in infants. For example, we have previously demonstrated that in infant rats during cold exposure, cardiac rate is directly related to their ability to produce heat endogenously. The primary source of endogenous heat production for infant rats is brown adipose tissue (BAT). Because of the dependence of cardiac rate on effective thermoregulation in the cold and because hypertension in spontaneously hypertensive rats (SHR) is influenced by the preweanling environment, in this study we examined the thermoregulatory and cardiac rate responses of infant SHR and Wistar-Kyoto rats (WKY) to varying levels of cold exposure. In experiment 1, 7- to 8-day-old SHR and WKY were acclimated at a thermoneutral air temperature (35 degrees C) and then exposed to successive decreases in ambient temperature (30.5 degrees C, 26.5 degrees C, 23 degrees C, and 17 degrees C) while thermal and metabolic measures were recorded. Although both strains increased BAT thermogenesis and oxygen consumption in response to cold exposure, SHR cooled more than WKY and exhibited lower levels of oxygen consumption at the lowest air temperatures. Experiment 2 was identical to experiment 1 except that cardiac rate was also measured. Again, SHR exhibited substantial thermoregulatory deficits compared with WKY; in addition, they were less able than WKY to maintain cardiac rate at the 2 lowest air temperatures tested. Finally, in experiment 3, infant SHR exhibited diminished BAT thermogenesis in response to a range of doses of a selective beta3-adrenoceptor agonist. We hypothesize that long-term thermoregulatory deficits during the early postnatal period influence cardiovascular function and contribute to the development of hypertension in SHR.


Asunto(s)
Aclimatación/fisiología , Tejido Adiposo Pardo/fisiología , Regulación de la Temperatura Corporal , Corazón/fisiología , Agonistas Adrenérgicos beta/farmacología , Animales , Regulación de la Temperatura Corporal/efectos de los fármacos , Frío , Dioxoles/farmacología , Frecuencia Cardíaca , Hipertensión/genética , Masculino , Consumo de Oxígeno , Ratas , Ratas Endogámicas SHR , Ratas Endogámicas WKY , Valores de Referencia , Especificidad de la Especie
13.
Behav Neurosci ; 113(6): 1274-82, 1999 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-10636306

RESUMEN

Two experiments explored the cardiovascular consequences of extreme cold exposure and their relationship with ultrasound production in infant rats. Experiment 1 addressed the thermoregulatory and cardiovascular concomitants of ultrasound production during cold exposure in rats pretreated with saline or the ganglionic blocker chlorisondamine (5 mg/kg). For both groups, emission of ultrasound was associated with hypothermia and bradycardia. Experiment 2 explored whether the hypothermia experienced by pups in Experiment 1 is associated with increased blood viscosity, which is an important factor affecting venous return to the heart. Blood viscosity increased significantly as temperature decreased from 38 degrees C to 22 degrees C. These experiments suggest that, during extreme cold exposure, decreased cardiac output and increased blood viscosity combine to diminish venous return. The authors have hypothesized that pups respond to decreased return by recruiting the abdominal compression reaction, a physiological maneuver that propels blood back to the heart, resulting in emission of ultrasound as an acoustic by-product.


Asunto(s)
Fenómenos Fisiológicos Cardiovasculares , Hipotermia Inducida , Vocalización Animal/fisiología , Animales , Viscosidad Sanguínea/fisiología , Bradicardia , Clorisondamina/administración & dosificación , Bloqueadores Ganglionares/administración & dosificación , Hemodinámica/fisiología , Masculino , Ratas , Ratas Sprague-Dawley
14.
Dev Psychobiol ; 33(2): 107-23, 1998 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-9742406

RESUMEN

The behavioral and physiological thermoregulatory capabilities of newborn and infant mammals have been studied for over half a century. Psychobiologists have noted that the infants of altricial species (e.g., rats) have physical and physiological limitations such that heat loss overwhelms heat production, thus forcing a reliance on behavioral thermoregulation for the maintenance of body temperature. Recent evidence, however, suggests that a modification of this view is justified. Specifically, throughout a range of moderately cold air temperatures, nonshivering thermogenesis by brown adipose tissue contributes significantly to the infant rat's behavioral and physiological adaptations to cold challenge. Given the prominent use of altricial species for the study of infant behavior, increased understanding of the infant's physiological responses to cold and the effect of thermal factors on behavior is warranted.


Asunto(s)
Animales Recién Nacidos , Conducta Animal/fisiología , Regulación de la Temperatura Corporal/fisiología , Mamíferos , Adaptación Fisiológica/fisiología , Tejido Adiposo Pardo/fisiología , Animales , Animales Recién Nacidos/clasificación , Animales Recién Nacidos/fisiología , Animales Recién Nacidos/psicología , Frío/efectos adversos , Mamíferos/clasificación , Mamíferos/fisiología , Mamíferos/psicología , Psicología Comparada/métodos , Psicología Comparada/normas , Ratas/fisiología , Ratas/psicología
15.
Behav Neurosci ; 112(3): 695-706, 1998 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-9676984

RESUMEN

It was previously hypothesized that brown adipose tissue (BAT) thermogenesis helps to maintain high rates of myoclonic twitching during cold exposure in infant rats (M. S. Blumberg & M. A. Stolba, 1996). To test this hypothesis, the sensitivity of twitching to various levels of cold exposure was assessed in week-old rats that were untreated or whose BAT thermogenesis was inhibited using a ganglionic blocker. Because week-old golden hamsters do not exhibit BAT thermogenesis, their sleep behaviors during cold exposure also were examined. Additional investigations in infant rats were conducted in which supplemental heat was provided to the interscapular region using a thermode and in which BAT was activated pharmacologically in ganglionically blocked pups. The results support the hypothesis that myoclonic twitching is sensitive to the prevailing air temperature and the activation of BAT thermogenesis.


Asunto(s)
Tejido Adiposo Pardo/fisiología , Animales Lactantes/fisiología , Regulación de la Temperatura Corporal/fisiología , Frío , Mioclonía , Sueño/fisiología , Tejido Adiposo Pardo/efectos de los fármacos , Animales , Regulación de la Temperatura Corporal/efectos de los fármacos , Clorisondamina/farmacología , Cricetinae , Femenino , Bloqueadores Ganglionares/farmacología , Modelos Lineales , Masculino , Mesocricetus , Contracción Muscular/fisiología , Mioclonía/etiología , Mioclonía/fisiopatología , Ratas , Sueño/efectos de los fármacos
16.
Am J Physiol ; 274(6): R1712-7, 1998 06.
Artículo en Inglés | MEDLINE | ID: mdl-9841546

RESUMEN

Previous research in infant rats suggested that brown adipose tissue (BAT), by providing warm blood to the heart during moderate cold exposure, protects cardiac rate. This protective role for BAT thermogenesis was examined further in the present study. In experiment 1, 1-wk-old rats in a warm environment were pretreated with saline or chlorisondamine (a ganglionic blocker), and then BAT thermogenesis was stimulated by injection with the beta3-agonist CL-316243. In experiment 2, pups were pretreated with chlorisondamine and injected with CL-316243, and after BAT thermogenesis was stimulated the interscapular region of the pups was cooled externally with a thermode. In both experiments, cardiac rate, oxygen consumption, and physiological temperatures were monitored. Activation of BAT thermogenesis substantially increased cardiac rate in saline- and chlorisondamine-treated pups, and focal cooling of the interscapular region was sufficient to lower cardiac rate. The results of these studies support the hypothesis that BAT thermogenesis contributes directly to the modulation of cardiac rate.


Asunto(s)
Tejido Adiposo Pardo/fisiología , Regulación de la Temperatura Corporal/fisiología , Frecuencia Cardíaca/fisiología , Agonistas Adrenérgicos beta/farmacología , Animales , Animales Recién Nacidos , Regulación de la Temperatura Corporal/efectos de los fármacos , Clorisondamina/farmacología , Dioxoles/farmacología , Bloqueadores Ganglionares/farmacología , Masculino , Ratas
17.
Physiol Zool ; 70(3): 324-30, 1997.
Artículo en Inglés | MEDLINE | ID: mdl-9231406

RESUMEN

Neonates of many mammalian species, including humans, depend primarily on thermogenesis by brown adipose tissue as a defense against cold challenge. Although the steady-state thermogenic responses of brown adipose tissue to various air temperatures are well known, the dynamic responses have received relatively little attention. In this article, we examine the relative stability of brown adipose tissue thermogenesis during brief perturbations of air temperature. Specifically, week-old rats were allowed to settle at one of two levels of cold exposure. These two levels were defined on the basis of previous work as being moderate (30.5 degrees C) or extreme (23 degrees C). After pups had settled at these temperatures, they were exposed to positive or negative air temperature perturbations of approximately 3.7 degrees C. Pups experiencing perturbations from the moderate air temperature, unlike those exposed to the extreme air temperature, exhibited organized thermogenic responses that allowed them to return quickly to their preperturbation conditions. These data suggest that brown adipose tissue thermogenesis is more stably controlled than has previously been suspected.


Asunto(s)
Tejido Adiposo Pardo/metabolismo , Animales Recién Nacidos/metabolismo , Regulación de la Temperatura Corporal , Frío , Animales , Temperatura Corporal , Femenino , Masculino , Consumo de Oxígeno , Ratas
18.
Am J Physiol ; 272(4 Pt 2): R1308-13, 1997 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-9140034

RESUMEN

Infants rats depend on heat production by brown adipose tissue (BAT) during cold challenge. Although it has been suggested that BAT thermogenesis protects the heart in the cold, the relationship of BAT activation to cardiac rate has not been examined directly. In the first experiment, the cardiac rate of 2- and 7- to 8-day-old rat pups was monitored during moderate and extreme cold challenge. Pups at both ages maintained cardiac rate during moderate cold challenge while BAT thermogenesis was increasing. In contrast, cooling to air temperatures at which BAT thermogenesis could increase no further resulted in pronounced bradycardia. In the second experiment, ganglionic blockade was used to eliminate BAT heat production and autonomic control of the heart in 7- to 8-day olds. Blockade suppressed BAT thermogenesis in the cold and led to pronounced decreases in interscapular temperature and cardiac rate. These data suggest that cardiac rate in infant rats is modulated both by the autonomic nervous system and BAT thermogenesis.


Asunto(s)
Aclimatación , Tejido Adiposo Pardo/fisiología , Envejecimiento/fisiología , Regulación de la Temperatura Corporal , Frecuencia Cardíaca , Consumo de Oxígeno , Tejido Adiposo Pardo/crecimiento & desarrollo , Animales , Animales Recién Nacidos , Temperatura Corporal , Frío , Electrocardiografía , Ganglios Autónomos/fisiología , Masculino , Ratas , Temperatura
19.
Dev Psychobiol ; 30(3): 181-94, 1997 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-9104549

RESUMEN

Previously, it was reported that week-old rats exposed to air temperatures that elicited submaximal levels of heat production (designated moderate cold exposure) remained asleep and did not vocalize (Blumberg & Stolba, 1996). In contrast, pups exposed to air temperatures that elicited maximal levels of heat production (designated extreme cold exposure) woke up and emitted ultrasonic vocalizations. We now report on the physiological and behavioral responses of pups in the transitional region between moderate and extreme air temperatures. Small decreases in air temperature across the transition resulted in pronounced decreases in physiological temperature and concomitant increases in ultrasound production. In a second experiment, it was shown that during moderate cold exposure respiratory frequency increased as air temperature decreased but, as extreme air temperatures were reached, respiratory frequency was maximized as ultrasound production began. The results from these two experiments illustrate how air temperatures that differ by as little as 2 degrees C can differentially modify the physiological and behavioral responses of neonates.


Asunto(s)
Regulación de la Temperatura Corporal/fisiología , Ultrasonografía , Animales , Animales Recién Nacidos , Conducta Animal , Laringe/fisiología , Masculino , Consumo de Oxígeno , Ratas , Ratas Sprague-Dawley , Temperatura , Vocalización Animal
20.
Brain Res ; 699(2): 214-20, 1995 Nov 20.
Artículo en Inglés | MEDLINE | ID: mdl-8616624

RESUMEN

Bignall, Heggeness and Palmer (1975) were the first to demonstrate increases in metabolic heat production following midpontine transection in neonatal rats. Subsequent work in adult rats has shown that this procedure disinhibits thermogenesis by brown adipose tissue (BAT). Bignall and his colleagues also found that hypothalamic ablation did not result in increased thermogenesis in 5-day-olds, leading them to conclude that thermoregulation depends on more caudal structures at that age. We have also found that midpontine transection disinhibits BAT thermogenesis and, furthermore, have extended that finding to newborn pups. When transections were made in the basal forebrain, however, we also found profound and rapid increases in brown fat thermogenesis. These results suggest the presence of at least two sources of inhibition of BAT thermogenesis in newborn rats: one located in the rostral pons-caudal midbrain and one located in the basal forebrain.


Asunto(s)
Tejido Adiposo/metabolismo , Regulación de la Temperatura Corporal/fisiología , Temperatura Corporal/fisiología , Prosencéfalo/metabolismo , Animales , Animales Recién Nacidos , Femenino , Masculino , Ratas , Ratas Sprague-Dawley , Factores de Tiempo
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