Effect of Supplementation With Omega-3 Fatty Acids, Magnesium, and Zinc on Canine Behavioral Disorders: Results of a Pilot Study.

Recent discoveries have shown that the chances of a dog developing a behavioral disorder may depend upon a number of factors including nutrition. The current pilot study was designed to provide an assessment of the efficacy of a dietary supplement containing omega-3 fatty acids, magnesium, and zinc on some common behavioral disorders in a population of Iranian domestic dogs. In total, 48 dogs including 6 dogs without any behavior disorder (control group) and 42 dogs with at least 1 common behavioral disorder, namely excessive activity, inappropriate elimination, fearfulness, destructiveness, and aggression toward unfamiliar people and dogs (test group), were given daily oral dose of gelatin capsules of fish oil supplements containing 330 mg eicosapentaenoic acid and 480 mg docosahexaenoic acid. Moreover, all dogs received 12-15 mg/kg of magnesium citrate and 5 mg/kg of zinc sulfate. Data were obtained using a questionnaire that dog owners were invited to fill out 2 times before (Days 0 and 42) and 2 times after the supplement treatment period (Days 84 and 126). The questionnaire asked owners whether their dog had exhibited any of the 6 common behavioral disorders on a 5-point Likert-like scale ranging from 0 (never or very rarely) to 4 (very often). The results showed no significant changes for any of the evaluated behavior disorders scale in the control group. In dogs with behavior disorders, results showed a significant reduction in the median score for the severity of fearfulness (P = .0083), destructiveness (P = .002), and inappropriate elimination (P < .001). In addition, there were no significant differences in the median score for the severity of excessive activity (P = .162), aggression toward dogs (P = .281), and aggression toward unfamiliar people (P = .09) during the course of the study. Results of the study reported here support the hypothesis that a combination of omega-3 fatty acids, magnesium, and zinc may improve some of the behavioral disorders.

Pharmacokinetics and effects of alfaxalone after intravenous and intramuscular administration to cats.

AIMS: To determine the pharmacokinetics, and anaesthetic and sedative effects of alfaxalone after I/V and I/M administration to cats. METHODS: Six European shorthair cats, three males and three females, with a mean weight of 4.21 (SD 0.53) kg and aged 3.8 (SD 0.9) years were enrolled in this crossover, two-treatment, two-period study. Alfaxalone at a dose of 5 mg/kg was administered either I/V or I/M. Blood samples were collected between 2-480 minutes after drug administration and analysed for concentrations of alfaxalone by HPLC. The plasma concentration-time curves were analysed by non-compartmental analysis. Sedation scores were evaluated between 5-120 minutes after drug administration using a numerical rating scale (from 0-18). Intervals from drug administration to sit, sternal and lateral recumbency during the induction phase, and to head-lift, sternal recumbency and standing position during recovery were recorded. RESULTS: The mean half-life and mean residence time of alfaxalone were longer after I/M (1.28 (SD 0.21) and 2.09 (SD 0.36) hours, respectively) than after I/V (0.49 (SD 0.07) and 0.66 (SD 0.16) hours, respectively) administration (p<0.05). Bioavailability after I/M injection of alfaxalone was 94.7 (SD 19.8)%. The mean intervals to sternal and lateral recumbency were longer in the I/M (3.73 (SD 1.99) and 6.12 (SD 0.90) minutes, respectively) compared to I/V (0 minutes for all animals) treated cats (p<0.01). Sedation scores indicative of general anaesthesia (scores >15) were recorded from 5-15 minutes after I/V administration and deep sedation (scores 11-15) at 20 and 30 minutes. Deep sedation was observed from 10-45 minutes after I/M administration. One cat from each group showed hyperkinesia during recovery, and the remainder had an uneventful recovery. CONCLUSIONS AND CLINICAL RELEVANCE: Alfaxalone administered I/V in cats provides rapid and smooth induction of anaesthesia. After I/M administration, a longer exposure to the drug and an extended half life were obtained compared to I/V administration. Therefore I/M administration of alfaxalone could be a reliable, suitable and easy route in cats, taking into account that alfaxalone has a slower onset of sedation than when given I/V and achieves deep sedation rather than general anaesthesia.

[Methylphenidate use in dogs with attention deficit hyperactivity disorder (ADHD). A case report of a Weimaraner bitch]. / Anwendung von Methylphenidat bei Hunden mit Aufmerksamkeitsdefizit-/Hyperaktivitätsstörung (ADHS). Fallbeschreibung am Beispiel einer Weimaranerhündin.

A 10-month-old Weimaraner bitch was presented at the practice exhibiting agitation, hyperactivity, inability to learn and attention deficit. The diagnostic findings were excessive, long-lasting acoustic and locomotory activity with unexpected inappropriate reactions. Hematological and biochemical blood analyses did not demonstrate abnormal findings. The first attempts at behavioral therapy and fluoxetine application were unsatisfactory. Therefore, a test was conducted with medication for central nervous system stimulation to confirm a diagnosis of hyperkinesis. Following the diagnosis of attention deficit hyperactivity disorder, the therapy was continued with behavioral modifications, with special consideration of rehabituation and resocialization as well as the use of methylphenidate. During the course of the therapy the bitch developed hyperactivity again when on heat. After changing the dosage of methylphenidate and additionally using dog appeasing pheromone, the behavior of the bitch became normal after 8 days. Two months later endoscopic ovarioectomy was performed. Twelve months after the initial use of methylphenidate the medication could be discontinued completely and the dog's behavior was normal. The methylphenidate dosage used during this therapy was much higher than recommended in the literature.

Use of naltrexone to antagonize high doses of remifentanil in cats: a dose-finding study.

OBJECTIVE: To determine the dose of naltrexone necessary to fully antagonize a high dose of remifentanil in cats. STUDY DESIGN: Prospective experimental study. ANIMALS: Six healthy adult cats weighing 4.9 ± 0.7 kg. METHODS: In a first phase, remifentanil (200 µg kg(-1) followed by 60 µg kg(-1) minute(-1) ) was administered intravenously to two cats, causing an increase in locomotor activity. Naltrexone (100 µg kg(-1) ) was then administered intravenously every minute until the increase in locomotor activity had been reversed. In a second phase, six cats were used. Baseline thermal threshold was determined, naltrexone (600 µg kg(-1) ) was administered intravenously and 30 minutes later thermal threshold determination repeated. Remifentanil (200 µg kg(-1) followed by 60 µg kg(-1) minute(-1) ) was administered intravenously and thermal threshold determination repeated at 60, 120, 180, and/or 240 minutes after naltrexone administration. Thermal threshold determinations were started shortly after the start of the continuous rate infusion (CRI) of remifentanil and this CRI was discontinued immediately after thermal threshold determination. If an increase in thermal threshold was found, naltrexone administration was repeated at decreasing intervals in the next experiment (all cats were not used for all dosing intervals). Experiments were repeated until a naltrexone dosing interval was found that prevented increases in thermal threshold for 4 hours in all six cats. RESULTS: In the first phase, both cats became severely dysphoric following remifentanil administration. A cumulative naltrexone dose of 300 µg kg(-1) was necessary to restore normal behavior in both cats. In the second phase, hourly administration of naltrexone (600 µg kg(-1) ) prevented increases in thermal threshold associated with hourly administration of remifentanil for 4 hours. Less frequent administration did not prevent increases in thermal threshold consistently. CONCLUSIONS: Hourly administration of naltrexone (600 µg kg(-1) ) antagonizes the behavioral and antinociceptive effects of a high dose of remifentanil in cats. CLINICAL RELEVANCE: Naltrexone may be useful for the treatment of opioid overdose in cats.

Zolpidem poisoning in a cat.

Zolpidem (Stilnox) is a non-benzodiazepine hypnotic drug of the imidazopyridine class intended for treatment of insomnia in humans. A 16-year-old neutered cat, weighing 3.8 kg, was presented with sudden onset of stupor, disorientation, severe ataxia, vomiting and hypersalivation. Symptomatic treatment was given when ingestion of 1.25 mg/kg zolpidem (half of a 10-mg tablet) was confirmed, because no information on the efficacy and safety of the use of flumazenil in the treatment of zolpidem poisoning in cats has been published to date. As zolpidem is prescribed with increasing frequency in humans, the occurrence of accidental poisonings of pets is likely to increase.

Group II metabotropic glutamate receptor antagonists LY341495 and LY366457 increase locomotor activity in mice.

The group II metabotropic glutamate receptor (mGluR) antagonists LY341495 and LY366457 were profiled for their effects on locomotor activity in mice. Both compounds significantly increased locomotor activity. Observational studies showed that rearing was also selectively increased. LY366457-induced hyperactivity was significantly attenuated by the selective D1 dopamine receptor antagonist SCH23390 and also by the D2 dopamine receptor antagonist haloperidol but only at doses that significantly suppressed spontaneous locomotion. The selective 5-HT(2A) antagonist MDL100907 had no effect on LY366457-induced hyperactivity, while the less selective 5-HT(2A-C) antagonist ritanserin had only a modest effect. In all cases, the doses of antagonists that reduced the locomotor response to LY366457 were greater than those previously shown to reduce the locomotor response to the psychostimulants amphetamine and cocaine and MK-801. Pretreatment with reserpine also significantly attenuated the response to LY366457, possibly implicating a monoaminergic substrate in the mediation of this effect. The phenomenonology and pharmacology of the locomotor activation induced by the mGluR antagonists differs markedly from that induced by locomotor stimulants such as amphetamine, cocaine or MK-801. These results suggest that group II mGluRs may be involved in the tonic suppression of locomotor and exploratory activity, and this suppression can be disinhibited in the presence of a group II mGluR antagonist.

Clinical syndrome associated with zolpidem ingestion in dogs: 33 cases (January 1998-July 2000).

Zolpidem is a nonbenzodiazepine hypnotic of the imidazopyridine class that is used to treat insomnia in humans. Zolpidem binds selectively to the benzodiazepine omega-1 receptor and increases the frequency of chloride channel opening, which results in inhibition of neuronal excitation. A retrospective study was conducted of zolpidem ingestion in dogs that were reported to the ASPCA Animal Poison Control Center (APCC) between January 1998 and July 2000. Data analysis included amount ingested, clinical effects, and time of onset of signs. Thirty-three reports of zolpidem ingestion in dogs (ranging in age from 5 months to 16 years) were evaluated. Approximate ingested dosages ranged from 0.24 to 21 mg/kg. Clinical signs reported included ataxia (18 dogs; 54.5%), hyperactivity (10 dogs; 30.3%), vomiting (7 dogs; 21.2%), and lethargy (5 dogs; 15.2%), as well as panting, disorientation, nonspecific behavior disorder, and hypersalivation (4 dogs each sign; 12.1%). Other signs reported include tachycardia, tremors, apprehension, vocalization, hypersalivation, weakness, and hyperesthesia. In 85% percent of reports, clinical signs developed within 1 hour and usually resolved within 12 hours. Although central nervous system (CNS) depression is reported as a primary effect of zolpidem in humans and would also be expected in dogs, information obtained from this study indicates that some dogs may exhibit a paradoxical excitation reaction. This effect appears to vary among individual dogs.

Hyperactivity and alopecia associated with ingestion of valproic acid in a cat.

A 1-year-old castrated male cat was evaluated because of alopecia of approximately 4 to 5 months' duration as well as hyperactive behavior. It was later determined that the cat was ingesting valproic acid by eating food to which it had been added for daily administration to a child in the household who had cerebral palsy. The clinical signs slowly resolved after the source of valproic acid was removed. This emphasizes the sensitivity of cats to drugs that are commonly used in humans. It was not determined whether the clinical signs that developed in this cat were caused by an adverse reaction or from toxicosis as a result of prolonged hepatic elimination of valproic acid, which requires glucuronide metabolism for disposition. However, the cat recovered completely following removal of the drug and prevention of further exposure. This report emphasizes the importance of obtaining a careful and complete history from the owner regarding an animal and its environment. In the cat of this report, the owner had not considered the impact of the presence of the drug in the child's food.

The red tide toxin, brevetoxin, induces embryo toxicity and developmental abnormalities.

Brevetoxins are lipophilic polyether toxins produced by the red tide dinoflagellate Gymnodinium breve, and their neurotoxic effects on adult animals have been documented. In this study, we characterized adverse developmental effects of brevetoxin-1 (PbTx-1) using an exposure paradigm that parallels the maternal oocyte transfer of toxin. Medaka fish (Oryzias latipes) embryos were exposed to PbTx-1 via microinjection of toxin reconstituted in a triolein oil droplet. Embryos microinjected with doses of 0.1-8.0 ng/egg (ppm) of brevetoxin-1 exhibited pronounced muscular activity (hyperkinesis) after embryonic day 4. Upon hatching, morphologic abnormalities were commonly found in embryos at the following lowest adverse effect levels: 1.0-3.0 ppm, lateral curvature of the spinal column; 3.1-3.4 ppm, herniation of brain meninges through defects in the skull; and 3.4-4.0 ppm, malpositioned eye. Hatching abnormalities were also commonly observed at brevetoxin doses of 2.0 ppm and higher with head-first, as opposed to the normal tail-first, hatching, and doses > 4.1 ng/egg produced embryos that developed but failed to hatch. Given the similarity of developmental processes found between higher and lower vertebrates, teratogenic effects of brevetoxins have the potential to occur among different phylogenetic classes. The observation of developmental abnormalities after PbTx-1 exposure identifies a new spectrum of adverse effects that may be expected to occur following exposure to G. breve red tide events.

Acetylcholine/dopamine interaction in planaria.

Planaria represents the most primitive example of centralization and cephalization of nervous system. Previous reports indicate that planaria shows specific behavioral patterns, analogous to mammalian stereotypes, in response to drugs acting on acetylcholine or dopamine transmission. Here we further characterized these responses, and investigated the interactions between cholinergic and dopaminergic systems by means of behavioral methods. Exposure to cholinergic agonists physostigmine or nicotine produced hypokinesia with 'bridge-like' and 'walnut' positions, respectively. Blockade of muscarinic receptors by atropine produced 'screw-like' hyperkinesia. Exposure to dopamine agonists (nomifensine, apomorphine) produced marked hyperkinesia with 'screw-like' movements. Finally, exposure to dopamine antagonists produced immobility or 'bridge-like' position. Pre-exposure to physostigmine blocked the behavioral effects of nomifensine and reduced and markedly delayed the behavioral effects of apomorphine. Pre-exposure to apomorphine slightly reduced and delayed the behavioral changes by physostigmine. Finally, planaria exposed to atropine after either SCH23388 or sulpiride showed 'C-like' or 'screw-like' hyperkinesia, respectively. Thus, reduction of cholinergic transmission seems to play a pivotal role in determining hyperkinesia in planaria. Under these conditions, different patterns of hyperkinetic activities occur, according to the subpopulation of dopamine receptors stimulated by drugs. These findings suggest that interactions between cholinergic and dopaminergic systems occur very early in animal phylogeny.