Interdog household aggression: 38 cases (2006-2007).

OBJECTIVE: To analyze factors associated with interdog household aggression and determine treatment outcomes. DESIGN: Retrospective case series and survey. Animals-38 pairs of dogs with interdog household aggression. Each pair of dogs was considered 1 case. PROCEDURES: Records of dogs with interdog household aggression that were examined during initial or follow-up consultations at a veterinary teaching hospital from December 5, 2006, to December 5, 2007, were analyzed for clinical features. Data regarding outcome, owner compliance, and efficacy of recommended treatments obtained by use of a follow-up survey were evaluated. RESULTS: Most cases (30/38 [79%]) of interdog household aggression involved same-sex pairs; 26 of 38 (68%) cases involved 1 female or a pair of females. Instigators and recipients of aggression were clearly identified in 27 of 38 (71%) cases; most instigators were the younger of the pair (20/27 [74%]) or were newer additions to the household (19/27 [70%]). Fight-eliciting triggers included owner attention, food, excitement, and found items. Some dogs had risk factors for behavior problems such as a history of living in multiple households (21/51 [41%]), adoption after 12 weeks of age (20/51 [39%]), or being acquired from a shelter (17/51 [33%]). Effective treatment recommendations included implementing a so-called nothing-in-life-is-free program, giving 1 dog priority access to resources, and administering psychotropic medication. Frequency and severity of fighting were significantly reduced after consultation. Owners reported a 69% overall improvement following treatment. CONCLUSIONS AND CLINICAL RELEVANCE: Most treatment strategies were considered effective. Consistency and predictability of social interactions are essential in resolving interdog household aggression.

The brain metabolic enhancer methylene blue improves discrimination learning in rats.

Methylene blue (MB) is a metabolic enhancer that has been demonstrated to improve memory retention when given post-training in low doses in a variety of tasks in rats, including inhibitory avoidance, spatial memory (in both normal and metabolically-impaired subjects), object recognition, and habituation to a familiar environment. MB has been also shown to improve memory retention of extinction of fear conditioning in the rat. No experiments have been conducted to determine the effects of MB on more complex learning such as in discrimination tasks that require repeated days of training. This study examined the effects of daily MB on spatial discrimination memory in a baited holeboard maze. Following three days of discrimination training, subjects treated daily with post-training MB (1 mg/kg) reliably discriminated between rewarded (baited) and non-rewarded (unbaited) trials as indicated by a greater number of correct responses on rewarded trials than non-rewarded trials during the last three days of discrimination training. No such discrimination effects were observed in the saline-treated control group during the same training period. To determine whether the memory-enhancing effects of MB are associated with an increase in metabolic energy capacity in the brain, cytochrome c oxidation was measured in brains from rats treated with 1 mg/kg MB or saline for three days. The number of daily injections was chosen based on the behavioral data which revealed group differences three days after the beginning of MB treatment. Brain cytochrome oxidase activity in the MB-treated group was approximately 70% higher than in saline-treated rats. The findings suggest that repeated post-training MB may improve memory consolidation between days of learning by an induction in the enzyme cytochrome oxidase, leading to increased metabolic capacity in brain regions requiring more energy during discrimination learning.

Methylene blue facilitates the extinction of fear in an animal model of susceptibility to learned helplessness.

The objectives were to (1) extend previous findings on fear extinction deficits in male congenitally helpless rats (a model for susceptibility to learned helplessness) to female congenitally helpless rats, and (2) attempt a therapeutic intervention with methylene blue, a metabolic enhancer that improves memory retention, to alleviate the predicted extinction deficits. In the first experiment, fear acquisition (four tone-shock pairings in operant chamber) was followed by extinction training (60 tones in open field). Congenitally helpless rats showed fear acquisition similar to controls but had dramatic extinction deficits, and did not display the gradual extinction curves observed in controls. Congenitally helpless rats demonstrated greater tone-evoked freezing as compared to controls in both the acquisition and extinction contexts one week after extinction training, and also in the extinction probe conducted one month later. In the second experiment (which began one month after the first experiment) congenitally helpless subjects were further exposed to tones for 5 days, each followed by 4 mg/kg methylene blue or saline IP, and had a fear renewal test in the acquisition context. Methylene blue administration improved retention of the extinction memory as demonstrated by significant decreases in fear renewal as compared to saline-administered congenitally helpless subjects. The impaired ability to extinguish fear to a traumatic memory in congenitally helpless rats supports the validity of this strain as an animal model for vulnerability to post-traumatic stress disorder, and this study further suggests that methylene blue may facilitate fear extinction as an adjunct to exposure therapy.

Methylene blue restores spatial memory retention impaired by an inhibitor of cytochrome oxidase in rats.

Cytochrome oxidase is the mitochondrial enzyme that catalyzes the utilization of oxygen for the electron transport chain during cellular respiration. Chronic subcutaneous infusion of sodium azide, an inhibitor of cytochrome oxidase, produced a spatial memory retention deficit in rats in a holeboard maze. Methylene blue, which has been shown to increase oxygen consumption in vitro, was used to restore mitochondrial electron transport in order to facilitate memory consolidation. Administration of 1 mg/kg methylene blue after training, during the memory consolidation period, completely restored the memory retention impaired by the inhibitor of cytochrome oxidase. This suggests that methylene blue may compensate for impaired mitochondrial respiration and improve spatial memory retention. Memory retention deficits found in some neurodegenerative diseases may be improved by drugs targeting impaired mitochondrial respiration.