Genetics of mouse behavior: interactions with laboratory environment.

Strains of mice that show characteristic patterns of behavior are critical for research in neurobehavioral genetics. Possible confounding influences of the laboratory environment were studied in several inbred strains and one null mutant by simultaneous testing in three laboratories on a battery of six behaviors. Apparatus, test protocols, and many environmental variables were rigorously equated.

Quantitative trait loci affecting risk for pentobarbital withdrawal map near alcohol withdrawal loci on mouse chromosomes 1, 4, and 11.

Barbiturate dependence is associated with the development of physiological dependence (withdrawal), tolerance, or a maladaptive pattern of drug use. Analysis of strain and individual differences with animal models for physiological dependence liability are useful means to identify potential genetic determinants of liability in humans. Behavioral and quantitative trait locus (QTL) mapping analyses were conducted with mice that are resistant versus sensitive to pentobarbital withdrawal.

Identifying genes for alcohol and drug sensitivity: recent progress and future directions.

New methods for identifying chromosomal regions containing genes that affect murine responses to alcohol and drugs have been used to identify many provisional quantitative trait loci (QTLs) since 1991. By 1998, 24 QTLs had been definitively mapped (P<5x10(-5)) to specific murine chromosomes, which indicates the presence of a relevant gene or genes at each location. The syntenic (homologous) region of the human genome for these genes is often known.

Chronic ethanol differentially alters susceptibility to chemically induced convulsions in withdrawal seizure-prone and -resistant mice.

Withdrawal seizure-prone (WSP) and withdrawal seizure-resistant (WSR) mice were selectively bred to have severe (WSP) or mild (WSR) handling-induced convulsions after chronic ethanol inhalation. The purpose of the present experiments was to determine whether seizure susceptibility differences between WSP and WSR mice during ethanol withdrawal were specific to agents acting at gamma-aminobutyric acidA or excitatory amino acid (EAA) receptors. Male WSP and WSR mice were exposed to ethanol vapor or air for 24 or 72 h.

High genetic susceptibility to ethanol withdrawal predicts low ethanol consumption.

C57BL/6J (B6) inbred mice are well known to drink large amounts of alcohol (ethanol) voluntarily and to have only modest ethanol-induced withdrawal under fixed dose conditions. In contrast, DBA/2J (D2) mice are "teetotallers" and exhibit severe ethanol withdrawal. Speculation that an inverse genetic relationship existed between these two traits was substantiated by meta-analysis of existing data collected in multiple genetic models, including large panels of standard and recombinant inbred strains, their crosses, and selectively bred mouse lines.

Identification of neuroendocrine-specific protein as an ethanol-regulated gene with mRNA differential display.

Chronic ethanol exposure produces changes in behavior that may result from effects of ethanol on gene expression. To identify potentially ethanol-regulated genes, mRNA differential display was used to screen the expressed genes in whole brain of mice chronically exposed to ethanol vapors. Mice genetically selected for susceptibility (Withdrawal Seizure-Prone; WSP) or resistance (Withdrawal Seizure-Resistant; WSR) to ethanol withdrawal convulsions were exposed to either ethanol vapor (ETOH group) or air (CTL group) for 72 h.

Magnetic resonance imaging of the wrist in early rheumatoid arthritis reveals a high prevalence of erosions at four months after symptom onset.

Objectives: To evaluate the role of magnetic resonance imaging (MRI) of the wrist in detecting early joint damage in patients with rheumatoid arthritis (RA).

Methods: MRI was performed on 42 patients with early RA (median symptom duration of four months). Scans were scored separately by two musculoskeletal radiologists using a newly devised scoring system, which was validated.

Drug withdrawal convulsions and susceptibility to convulsants after short-term selective breeding for acute ethanol withdrawal.

High Alcohol Withdrawal (HAW) and Low Alcohol Withdrawal (LAW) mice were selectively bred from a foundation population of C57BL6/J (B6) x DBA/2J (D2) F2 intercross progeny for display of intense or mild handling-induced withdrawal convulsions, respectively, following a single injection of a hypnotic dose of ethanol (alcohol; 4 g/kg). The HAW line had significantly greater alcohol withdrawal severity scores compared to the LAW line after only a single generation of selection; the magnitude of the line difference was 8-fold by the fourth selected generation. We tested these lines for severity of withdrawal convulsions following the benzodiazepine, diazepam; the gaseous anesthetic, nitrous oxide; the imidazopyridine, zolpidem and the barbiturate, pentobarbital.

Genetic determinants of sensitivity to diazepam in inbred mice.

Mice from 15 standard inbred strains were tested for sensitivity to several effects of acute diazepam (DZ). Strains differed in sensitivity to DZ-induced: low-dose stimulation and high-dose depression of locomotor activity, hypothermia, and ataxia assessed on a rotarod. Correlations among strain means indicated that sensitivity to a particular effect of DZ generalized well across doses.

Provisional mapping of quantitative trait loci for chronic ethanol withdrawal severity in BXD recombinant inbred mice.

Male mice from C57BL/6J (B6), DBA/2J (D2) and their 25 recombinant inbred (RI) strains were exposed to ethanol (EtOH) vapor (3.0-9.0 mg EtOH/liter of air) for 72 hr.

Increased vulnerability to cocaine in mice lacking the serotonin-1B receptor.

There is increasing evidence that genetic factors can influence individual differences in vulnerability to drugs of abuse. Serotonin (5-hydroxytryptamine, 5-HT), acting through many receptors can modulate the activity of neural reward pathways and thus the effects of various drugs of abuse. Here we examine the effects of cocaine in mice lacking one of the serotonin-receptor subtypes, the 5-HT1B receptor.

Acute exercise reduces caffeine-induced anxiogenesis.

Purpose: This experiment examined the influence of acute exercise on anxiety following caffeine-induced elevations in self-rated anxiety.

Methods: Eleven physically active, moderately fit males aged 25.1 +/- 3.

Late development of resistance to bromocriptine in a patient with macroprolactinoma.

We report the case of a man with an invasive macroprolactinoma who developed resistance to bromocriptine to which he had previously responded satisfactorily for 5 years. Subsequently, hyperprolactinemia was controlled equally well with 600 microg quinagolide daily and later with 4.5 mg cabergoline weekly.

Ethanol, body temperature and thermoregulation.

1. The effects of ethanol on body temperature (Tb) and on the regulator of Tb are reviewed. 2.

Genetic determinants of morphine activity and thermal responses in 15 inbred mouse strains.

Mice from 15 standard inbred strains were tested for sensitivity to two effects of acute morphine administration, open-field activity, and body temperature changes, at doses of 0, 4, 8, 16, and 32 mg/kg, I.P. Large strain differences were consistently observed, indicating a substantial degree of genetic determination of these traits.

Ethanol disrupts and decreases the regulated body temperature differentially in C57BL/6J and DBA/2J mice.

Two inbred mouse strains, C57BL/6J (B6) and DBA/2J (D2), were evaluated for effects of ethanol on thermoregulation. Continuous recording of core temperature (Tc) from undisturbed animals at an ambient temperature (Ta) of 27 degrees C indicated Tc was similar for both strains during active (approximately 38.0 degrees C) and inactive (approximately 36.

Behavioral phenotypes of inbred mouse strains: implications and recommendations for molecular studies.

Choosing the best genetic strains of mice for developing a new knockout or transgenic mouse requires extensive knowledge of the endogenous traits of inbred strains. Background genes from the parental strains may interact with the mutated gene, in a manner which could severely compromise the interpretation of the mutant phenotype. The present overview summarizes the literature on a wide variety of behavioral traits for the 129, C57BL/6, DBA/2, and many other inbred strains of mice.

Quantitative trait loci involved in genetic predisposition to acute alcohol withdrawal in mice.

Alcohol dependence (alcoholism) is accompanied by evidence of tolerance, withdrawal (physiological dependence), or compulsive behavior related to alcohol use. Studies of strain and individual differences using animal models for acute physiological dependence liability are useful means to identify potential genetic determinants of liability in humans. Behavioral and quantitative trait analyses were conducted using animal models for high risk versus resistance to acute physiological dependence.

Quantitative trait loci affecting methamphetamine responses in BXD recombinant inbred mouse strains.

Individual differences in most behavioral and pharmacological responses to abused drugs are dependent on both genetic and environmental factors. The genetic influences on the complex phenotypes related to drug abuse have been difficult to study using classical genetic analyses. Quantitative trait locus (QTL) mapping is a method that has been used successfully to examine genetic contributions to some of these traits by correlating allelic variation in polymorphic genetic markers of known chromosomal location with variation in drug-response phenotypes.

Exploring alcohol withdrawal syndrome.

Alcohol withdrawal syndrome is characterized by hyperactivity of the nervous system. This hyperactivity represents the brain's attempt to function normally despite the inhibitory effect of chronic alcohol consumption. The syndrome manifests when alcohol consumption ceases.

Sensitivity to ethanol-induced ataxia in HOT and COLD selected lines of mice.

Studies with inbred strains of mice have suggested that there may be a genetic correlation between strain sensitivities to the ataxic and hypothermic responses to ethanol (EtOH), which would suggest that some genes influence both responses. To test this hypothesis, EtOH sensitivity was determined in replicate lines of mice selectively bred for sensitivity (COLD) or resistance (HOT) to acute ethanol hypothermia. Several tests were used to index ataxia, related traits such as muscle strength, and locomotor activity.