During the past decade, the zebrafish has emerged as a leading model for mechanistic cancer research because of its sophisticated genetic and genomic resources, its tractability for tissue targeting of transgene expression, its efficiency for forward genetic approaches to cancer model development, and its cost effectiveness for enhancer and suppressor screens once a cancer model is established. However, in contrast with other laboratory animal species widely used as cancer models, much basic cancer biology information is lacking in zebrafish. As yet, data are not published regarding dietary influences on neoplasm incidences in zebrafish. Little information is available regarding spontaneous tumor incidences or histologic types in wild-type lines of zebrafish. So far, a comprehensive database documenting the full spectrum of neoplasia in various organ systems and tissues is not available for zebrafish as it is for other intensely studied laboratory animal species. This article confirms that, as in other species, diet and husbandry can profoundly influence tumor incidences and histologic spectra in zebrafish. We show that in many laboratory colonies wild-type lines of zebrafish exhibit elevated neoplasm incidences and neoplasm-associated lesions such as heptocyte megalocytosis. We present experimental evidence showing that certain diet and water management regimens can result in high incidences of neoplasia and neoplasm-associated lesions. We document the wide array of benign and malignant neoplasms affecting nearly every organ, tissue, and cell type in zebrafish, in some cases as a spontaneous aging change, and in other cases due to carcinogen treatment or genetic manipulation.

The zebrafish, Danio rerio, has become a major model organism used in biomedical studies. The widespread use of Danio rerio in research laboratories requires a comprehensive understanding of the husbandry of this species to ensure efficient propagation and maintenance of healthy and genetically diverse colonies. Breeding is a key element in zebrafish husbandry. It is a complex process influenced by a number of factors. Mate choice and mating behavior depend, for example, on olfactory cues, visual stimuli, and social interactions. Spawning is affected by the age and size of fish, interval at which fish are used for egg production, light cycle, diet, and fish health status. A number of breeding strategies, based on either single-pair matings or group crosses, are commonly employed in the laboratory to propagate lines and to identify carriers of specific mutations and/or transgenes. Propagation of zebrafish lines, in particular wild-type-derived strains, is closely monitored to ensure that genetic diversity and vigor are maintained. A robust zebrafish line typically carries a large number of polymorphic variations, which may interfere with reproducibility of experiments. To get a better insight into these variations, a wild-type hybrid Sanger AB Tübingen line has been generated from sequenced homozygous founders.

The use of translational noninvasive neuroimaging has revealed that drug addiction and obesity share striking similarities in functional impairment in discrete brain regions and neurotransmitter circuits. Imaging experiments in both humans and rodents (using complementary experimental designs) show similar abnormalities in brain glucose metabolism in the prefrontal cortex (involved in inhibitory control) and hippocampus (memory) as well as impairments in dopamine signaling in the striatum (involved in food and drug reward, goal orientation, motivation, and habit formation). In both species, many of these observations have been obtained through concurrent and parallel monitoring of both brain activity and behavioral manifestations during drug administration, food sensory (visual, olfactory) stimulation, and craving. This review aims to show that noninvasive brain imaging strategies such as small animal positron emission tomography offer significant potential and promise for modeling motivational disorders such as drug addiction and obesity in humans. Rodent addiction models will prove valuable for understanding brain responses to drug cues and will help guide treatment, especially in relapse situations triggered by exposure to conditioned drug cues.

The review articles in this issue describe animal models (predominantly rodents) that have contributed to monumental progress and advancement of knowledge in the fi eld of addictive and neurobiological behavior research (ANBR 1 ). This article provides brief guidance to institutional animal care and use committee (IACUC) members for their review of ANBR protocols involving animal models, with an emphasis on rodent models. In addition to the 2011 Guide for the Care and Use of Laboratory Animals (NRC 2011; the Guide), researchers and IACUC members must ensure compliance with the requirements of the Public Health Service Policy (implemented under the NIH Offi ce of Laboratory Animal Welfare), the United States Department of Agriculture (USDA) Animal Welfare Act, and the Association for the Accreditation and Advancement of Laboratory Animal Care (AAALAC) International.

Confinement in metabolism pens may provoke a stress response in alpacas that will reduce the welfare of the animal and jeopardize the validity of scientific results obtained in such pens. In this study, we tested a protocol designed to successfully train alpacas to be held in a specially designed metabolism pen so that the animals' confinement would not jeopardize their welfare. We hypothesized that the alpacas would show fewer behaviors associated with a response to stress as training gradually progressed, and that they would adapt to being in the confinement of the metabolism pen. The training protocol was successful at introducing alpacas to the metabolism pens, and it did reduce the incidence of behavioral responses to stress as the training progressed. The success of the training protocol may be attributed to the progressive nature of the training, the tailoring of the protocol to suit alpacas, and the use of positive reinforcement. This study demonstrated that both animal welfare and the validity of the scientific outcomes could be maximized by the gradual training of experimental animals, thereby minimizing the stress imposed on the animals during experimental procedures.

Mongolian gerbils (Meriones unguiculatus) have an incomplete circle of Willis (CoW), as a result of which approximately 30-40% of these animals develop focal cerebral ischemia after unilateral carotid occlusion (UCO). There are four types of patterns of the anterior and posterior communicating arteries (ACoAs and PCoAs, respectively) of the CoW and they determine the severity of the ischemic symptoms. We used 398 gerbils from five generations, including a selectively bred ischemia-prone group, to investigate post-UCO ischemic symptoms and possible correlations of ACoA and PCoA patterns between parents and their progeny. We observed that if the parents had complete ACoAs, their progeny also had complete ACoAs, and we found significant differences when the parents' ACoAs were incomplete: in 60.4% of offspring the type of ACoA was consistent with that of the mother and in 48.2% it was consistent with that of the father. The severity of the neurological symptoms after UCO was significantly related to the patterns of the ACoAs when PCoAs were absent. The proportion of UCO ischemia in gerbils with incomplete ACoAs was significantly higher than in those with complete ACoAs. After selectively breeding five generations, the proportion of UCO ischemia increased from 40% in the F1 animals to 75% in the F5 animals. Our results suggest that variations in the CoW are genetic and demonstrate that we successfully established an ischemia-prone group of gerbils.

Marijuana (Cannabis sativa) is the most commonly used illicit drug worldwide as well as in the Unites States. Prolonged use of marijuana or repeated administration of its primary psychoactive constituent, Δ9-tetrahydrocannabinol (THC), can lead to physical dependence in humans and laboratory animals. The changes that occur with repeated cannabis use include alterations in behavioral, physiological, and biochemical responses. A variety of withdrawal responses occur in cannabis-dependent individuals: anger, aggression, irritability, anxiety and nervousness, decreased appetite or weight loss, restlessness, and sleep difficulties with strange dreams. But the long half-life and other pharmacokinetic properties of THC result in delayed expression of withdrawal symptoms, and because of the lack of contiguity between drug cessation and withdrawal responses the latter are not readily recognized as a clinically relevant syndrome. Over the past 30 years, a substantial body of clinical and laboratory animal research has emerged supporting the assertion that chronic exposure to cannabinoids produces physical dependence and may contribute to drug maintenance in cannabis-dependent individuals. However, no medications are approved to treat cannabis dependence and withdrawal. In this review, we describe preclinical and clinical research that supports the existence of a cannabinoid withdrawal syndrome. In addition, we review research evaluating potential pharmacotherapies (e.g., THC, a variety of antidepressant drugs, and lithium) to reduce cannabis withdrawal responses and examine how expanded knowledge about the regulatory mechanisms in the endocannabinoid system may lead to promising new therapeutic targets.

It’s a great pleasure to be here and to be able to share with you some of the experiences of one institution, the Uni­ versity of Alabama at Birmingham. I came into the field of lab animal medicine in the late 1970s. Today’s presentation will focus on events, particu­ larly at UAB, starting in the mid-90s. We’d [gone] along from the mid-80s on a pretty steady state until the mid-90s and suddenly our animal use took off. For those of you who may not know the term “care days,” it’s like “hospital beds.” We’re talking about units: one box of mice kept 30 days would be 30 care days or 30 boxes of mice kept 1 day would be 30 care days. We’re talking about millions of care days. At the same time, we were losing ground in terms of space. We had some new facilities designed but when we projected our use, we’d be falling short, both short term and long term. Several other factors were affecting this besides physical space. We had rapidly growing rodent populations. We had a lot greater use of genetically altered or immuno­ compromised animals. We had a change in animal models. I’m sure all of you at institutions are aware of this—you re­ cruit a new investigator, recruit a new research team, open a new department, and it’s a whole new world. We were hav­ ing to deal with studies that required better control of light­ ing, temperature, the use of hazardous agents, as well as the use of magnetic resonance (MRI) and other imaging tech­ nologies. We also had out-of-date facilities and equipment. I hasten to add that we were AAALAC accredited and were able to maintain those standards. But subtle issues with the facilities were impacting us. We had a lot of diffi culty in maintaining conditions—Chris mentioned the HVAC (heat­ ing, ventilation, and air conditioning), and that was certainly something we struggled with. The animal care folks and re­ search personnel didn’t like working in some of the facili­ ties. I remember our largest facility had just one stall for women in the rest room. The women didn’t have locker rooms and it wasn’t a nice place to work.