Dopamine receptor sensitivity after chronic dopamine agonists. Striatal 3H-spiroperidol binding in mice after chronic administration of high doses of apomorphine, N-n-propylnorapomorphine and dextroamphetamine.

Several previous reports have demonstrated that chronic administration of both directly and indirectly acting dopamine agonists produces a supersensitive behavioral response to challenge doses of dopamine agonists when compared to the responses induced by acute administration of these drugs. That is, a given dose of a dopamine agonist will produce a greater response after chronic dopamine agonist treatment than is observed upon acute administration of that dose. A similar behavioral phenomenon resulting from chronic administration of dopamine antagonists has been suggested to be due to an increase in the number of dopamine receptors present in relevant brain areas. The same hypothesis has been put forward for the hypersensitivity induced by chronic dopamine agonist administration. The present study was designed to investigate the effect of chronic administration of high doses of both direct and indirect dopamine agonists on the dopamine receptors labeled by 3H-spiroperidol. Groups of animals (CD-1 mice) were sacrificed 1, 3 and 5 days following the last chronic injection. Striatal tissue from these mice was incubated with 3H-spiroperidol and dopamine receptor binding evaluated. Affinity of the receptors for the ligand was unaltered by treatments. The receptors labeled by 3H-spiroperidol showed no significant differences in number following the chronic administration of high doses of apomorphine (30 mg/kg). The Bmax was significantly decreased at only one time period following chronic administration of dextroamphetamine (4 mg/kg); however, there was a dramatic 30% reduction in the Bmax in striatal tissue from those mice treated with N-n-propylnorapomorphine. These results suggest that the hypersensitive behavioral response in mice following chronic administration of direct and indirect acting dopamine agonists is not due to an increase in the number of dopamine receptors in the striatum which are labeled by 3H-spiroperidol.

Characterization of leukotriene B4 synthesis in canine polymorphonuclear leukocytes.

The synthesis and release of leukotriene B4 (LTB4) from canine polymorphonuclear leukocytes (PMNs) was characterized in terms of incubation time, temperature and effects of calcium ionophore A23187 concentrations. Maximal LTB4 concentrations were determined when canine PMNs were incubated with 10 microM A23187. Increasing LTB4 concentrations were determined through 10 min incubation. The maximal LTB4 concentrations (310 +/- 30 pg LTB4/2.5 x 10(5) cells) determined at 10 min did not change through a 55 min incubation period. Greater LTB4 concentrations were synthesized by canine PMNs at 37 degrees C (268 +/- 12 pg LTB4/2.5 x 10(5) cells) than at 25 degrees C (206 +/- 11 pg LTB4/2.5 x 10(5) cells) or 5 degrees C (59 +/- 3 pg LTB4/2.5 x 10(5) cells). The synthesis of LTB4 in canine PMNs was inhibited by incubation of the cells with either of two known lipoxygenase inhibitors, BWA4C or BW755C. BWA4C inhibited LTB4 synthesis with an approximate IC50 = 0.1 microM, whereas BW755C inhibited LTB4 synthesis with an approximate IC50 = 10 microM. These results indicate canine PMNs have the capability to synthesize large quantities of LTB4 when stimulated with calcium ionophore A23187. Furthermore, the 5-lipoxygenase inhibitors BWA4C, an acetohydroxyamic acid, and BW755C, a phenyl pyrazoline, can readily inhibit LTB4 synthesis in canine PMNs.

Elevation of thromboxane in pressure wounds.

Arachidonic acid metabolites have been implicated as mediators of progressive dermal ischemia. Decubitus ulcer formation results from chronic mechanical pressure on the skin which results in a diminished blood supply to the skin and underlying tissues. To evaluate the role of thromboxanes in pressure wounds, we measured TxB2, a stable metabolite of TxA2, in spontaneously occurring pressure wounds on Greyhound dogs. In pressure wounds in which the skin was showing early signs of pressure necrosis but was still intact, elevated TxB2 concentrations were found in healthy appearing tissues immediately adjacent to the pressure wounds, in the inner edge of the wounds, and in the center of the wounds. Significantly greater TxB2 concentrations (P less than 0.05) were found in the center of the intact wounds versus the TxB2 concentrations in the inner edge of the wounds or in healthy appearing tissues adjacent to the wounds. In pressure wounds in which the center of the wound had ulcerated or had an eschar, elevated TxB2 concentrations were found in tissues in the inner edge of the wounds and in healthy appearing tissues immediately adjacent to the pressure wounds. These results demonstrate the occurrence of elevated thromboxane concentrations in and around spontaneously occurring pressure wounds.

Reactive capacity: a sensitive behavioral marker of movement initiation and nigrostriatal dopamine function.

Thirty-two Long Evans male rats with sham operations or unilateral 6-OHDA-induced damage to meso-telencephalic dopaminergic neurons were evaluated on a reactive capacity task that demanded high speed movement initiation. The task required lever manipulation to avoid signalled shock. The interval between the warning and the shock was incrementally reduced. A one-sleeved vest provided the opportunity to measure movement initiation of each limb independently. Extent of lesion was assessed by [3H]DA uptake, [3H]spiroperidol binding, or DA levels. Movement initiation latencies for each forelimb were found to be linearly related to interhemispheric striatal DA asymmetry induced by microinjections of 6-OHDA. Even those lesions resulting in small to moderate decreases in DA function, including deficits causing no chronic posture or sensory asymmetries, resulted in reactive capacity deficits and greatly slowed reaction time in the paw contralateral to the lesion. Following severe lesions, small yet substantial deficits were also seen in ipsilateral paw performance, which may be related to DA depletions found in the non-lesioned striatum. Thus, a reactive capacity task which requires the animal to react with maximal speed appears to be a potentially good index of nigrostriatal dopamine integrity even when the depletion is not severe.

Behavioral sensitization following subchronic apomorphine treatment--possible neurochemical basis.

Subchronic treatment with the dopamine agonist apomorphine produces a sensitization to the stereotypic effects of subsequent apomorphine challenge. The present study investigated the effects of this subchronic treatment on apomorphine induced stereotypic behavior and striatal dopamine synthesis, release, metabolism, and D2 receptor binding. The pretreatment, which enhanced the behavioral response to apomorphine challenge, also elevated basal dopamine synthesis and metabolism, but left the ability of a challenge dose of apomorphine to inhibit dopamine synthesis and metabolism unaltered. Thus, ongoing dopamine synthesis and extracellular levels of metabolites would be higher following apomorphine challenge in animals treated subchronically with the agonist. In contrast, neither synaptosomal dopamine release in response to depolarizing stimuli nor the density of D2 dopamine receptors was altered by the treatment. Overall, the results suggest that, while we did not find evidence of autoreceptor desensitization per se, apomorphine treatment may result in enhanced extracellular dopamine levels following dopamine agonist challenge to provide a greater stimulation of an intact dopamine receptor system.

Behavioral sensitization following a single apomorphine pretreatment--selective effects on the dopamine release process.

Once daily subchronic pretreatments with the dopamine (DA) agonist apomorphine (APO) increase striatal DA synthesis and metabolism. Such changes imply that adaptations to APO do not dissipate completely within 24 h. In the present report we evaluated the effects of a single APO treatment 24 h prior to euthanasia on behavior and on striatal DA synthesis, metabolism, release and receptor binding. The single APO pretreatment reduced DA release from striatal synaptosomes. In contrast, striatal DA synthesis, metabolism, and the high-affinity binding of DA to the D2 receptor were unaltered 24 h after agonist pretreatment. At this time the stereotypic response to a subsequent APO challenge was enhanced. This adaptive pattern is different from that observed 60 min following an acute APO pretreatment, when high-affinity D2 binding is reduced. The pattern 24 h following a single APO pretreatment is also different from that observed following subchronic agonist dosing, when stereotypic behavior is enhanced, while basal DA synthesis and metabolism are increased.

Posture-independent sensorimotor analysis of inter-hemispheric receptor asymmetries in neostriatum.

Nigrostriatal dopaminergic neurons are thought to be critically important for somato-sensorimotor behavior. Following unilateral irreversible elimination of these neurons, an animal shows an ipsiversive postural bias and permanently fails to orient its head toward tactile stimuli placed on the contralateral side of the body. In response to apomorphine, a dopamine agonist, these rats display contraversive circling. This effect is thought to reflect denervation-induced proliferation of dopamine receptors in the ipsilateral striatum. We have developed a sensitive procedure that measures sensorimotor function independent of postural and circling biases. We record the latencies to remove small pieces of adhesive stimuli placed onto the snout or radial surface of the forelimbs. The stimuli are placed symmetrically and simultaneously, which is analogous to tactile-extinction procedures used clinically. In the first study we found that rats with unilateral 6-hydroxydopamine (6-OHDA)-induced lesions of the nigrostriatal pathway showed a contralateral sensorimotor bias in response to doses of apomorphine below those necessary to produce contraversive circling. In a second study, unilateral striatal microinjections of kainic acid (KA) were used to destroy the neurons on which the postsynaptic dopaminergic receptors of the nigrostriatal system are contained. Compared to 6-OHDA, KA produced unexpected results in standard orientation tests. None of the KA-treated rats showed contralateral neglect, and some even showed ipsilateral deficits. However, the standard orientation tests are confounded by postural asymmetries, which were irregular in the KA-treated group. Using again the posture-independent sensorimotor procedure, we found that all KA-treated rats, like the 6-OHDA-treated rats, uniformly displayed ipsilateral sensorimotor biases. Sensorimotor function relating to inter-striatal asymmetries may be more specifically assessed with the bilateral-adhesive tests.

Analysis of neurotransmitter metabolite concentrations in canine cerebrospinal fluid.

The concentrations of dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), and 5-hydroxyindole-3-acetic acid (5-HIAA) in CSF obtained from the cisterna magna of 21 nonneurologically compromised dogs were determined by high-pressure liquid chromatography and electrochemical detection. A rapid method of sample preparation, which involved single filtration through a deproteinizing membrane, was used. Canine CSF obtained in this manner contained 5.78 +/- 0.78 ng of DOPAC/ml, 72.19 +/- 4.09 ng of HVA/ml, and 29.95 +/- 1.67 ng of 5-HIAA/ml. Linear regression analysis between HVA and 5-HIAA yielded a correlation coefficient of 0.4804. The neurotransmitter index, HVA/5-HIAA, was found to be more indicative of the dopaminergic metabolite HVA than the acid metabolite of serotonin, 5-HIAA (correlation coefficient with HVA = 0.5529 vs a correlation coefficient with 5-HIAA = -0.4462). A poor relationship (correlation coefficient = -0.1715) was found to exist between the 2 dopaminergic metabolites DOPAC and HVA in the CSF.

A rostrocaudal gradient for neurotransmitter metabolites and a caudorostral gradient for protein in canine cerebrospinal fluid.

Neurotransmitter metabolites (dihydroxyphenylacetic acid [DOPAC], homovanillic acid [HVA], and 5-hydroxyindoleacetic acid [5-HIAA]) in CSF of 10 healthy dogs were evaluated with reverse-phase high-pressure liquid chromatography and electrochemical detection. Neurotransmitter metabolite concentrations determined in CSF collected from the cisterna magna were compared with those values in CSF collected from the lumbar dorsal subarachnoid space. Amounts of DOPAC (P = 0.0444), HVA (P = 0.0001), and 5-HIAA (P = 0.0316) were significantly lower in lumbar spinal fluid compared with those values in the cervical spinal fluid. Metabolite concentrations in cervical and lumbar CSF were: DOPAC = 2.81 +/- 0.73 ng/ml of CSF and 1.28 +/- 0.57 ng/ml; HVA = 98.29 +/- 12.42 ng/ml and 4.68 +/- 1.61 ng/ml; and 5-HIAA = 46.29 +/- 8.17 ng/ml and 36.96 +/- 4.07 ng/ml, respectively. Cytologic evaluations of cervical and lumbar CSF revealed a similar concentration of 3 +/- 1 WBC/microliters in both fluids. A significant (P = 0.0002) difference in protein concentration between the 2 regions was observed, with 16.1 +/- 1.8 mg of protein/dl in the cervical CSF and 27.2 +/- 2.3 mg of protein/dl in the lumbar CSF. Between the cisterna magna and lumbar dorsal subarachnoid space of dogs, a rostrocaudal gradient existed for neurotransmitter metabolites, and a caudorostral gradient existed for protein.

Evaluation of the dermal effects of cast padding in coaptation casts on dogs.

Three configurations of cast padding and no cast padding were evaluated for their effects on skin in dogs. Padding was placed over bony prominences, between bony prominences, and over both areas for full-length padding under short-limb walking casts applied to 1 pelvic limb of Greyhounds. Evaluations were performed by pressure measurement over the calcaneal tuberosity, measurement of skin thromboxane B2 (TxB2) concentrations in skin over bony prominences, and measurement of plasma TxB2 concentrations. Pressure studies were performed to evaluate cutaneous pressures related to no cast padding and various configurations of cast padding. Concentrations of TxB2 in the skin were determined to evaluate the skin inflammatory effects of no padding and the padding configurations, and TxB2 concentrations in the plasma were analyzed to ascertain whether they could be used to predict impending dermal pressure lesions. Flexion of casted limbs revealed the greatest pressure over the calcaneal tuberosity with full-length cast padding. This was followed in decreasing order by no cast padding, padding over the prominences, and padding between the prominences. Compared with all other bony prominences and padding configurations, TxB2 skin concentrations were significantly higher over the calcaneal tuberosity when no padding was used and over the lateral base of metatarsal V when padding was placed between the prominences. Over the calcaneal tuberosity, this was attributed to the sharpness of the prominence and its potential for movement. This high TxB2 concentration corresponded to the high pressure found in the pressure studies. Over the lateral base of metatarsal V, the increase in TxB2 concentration was related to the mass of the prominence and the tendency for localized padding to settle around the area.(ABSTRACT TRUNCATED AT 250 WORDS)

Evaluation of the effects of omega-3 fatty acid-containing diets on the inflammatory stage of wound healing in dogs.

OBJECTIVES: To ascertain the effects of dietary omega-3 (n-3) fatty acids on biochemical and histopathologic components of the inflammatory stage of wound healing. ANIMALS: 30 purpose-bred Beagles. PROCEDURE: Dogs were allotted to 5 groups of 6. Each group was fed a unique dietary fatty acid ratio of omega-6 to n-3--diet A, 5.3:1; diet B, 10.4:1; diet C, 24.1:1; diet D, 51.6:1; and diet E, 95.8:1. Dogs were fed once daily for 12 weeks, then biopsy specimens were taken from 4-day-old wounds of each dog and analyzed by gas chromatography-mass spectrometry for: prostaglandin E2 (PGE2) metabolites, and ratios of omega-6 to n-3 fatty acids, arachidonic acid (AA) to eicosapentaenoic acid (EPA), adrenic acid to docosahexaenoic acid, and PGE2 to prostaglandin E3 (PGE3) metabolites. RESULTS: Qualitative analysis was carried out on AA, EPA, adrenic acid, docosahexaenoic acid, and the major metabolite from the PGE2 and PGE3 pathway. These molecules were further quantified with respect to diet to determine significant differences. By analysis of the AA-to-EPA ratio, diet A was different from diets D and E and diets B and C were different from diet E (P < 0.05). By analysis of the PGE2-to-PGE3 metabolite ratio, diet A was different from diet E (P < 0.05). Though biochemical analysis indicated dietary dependence, histopathologic data indicated no significant difference with respect to diet groups. CONCLUSION: The biochemical component of the inflammatory stage of wound healing can be manipulated by diet. CLINICAL RELEVANCE: Omega-3 fatty acid-enriched diets can be used to control inflammation associated with dermatologic conditions.

Effect of locally injected medications on healing of pad wounds in dogs.

OBJECTIVE: To ascertain the effects of locally injected immunostimulant and tripeptide-copper complex (TCC) on improving healing of pad wounds. DESIGN: Wounds in pads of large dogs were injected with either medication or physiologic saline solution (controls). Healing was evaluated. ANIMALS: 12 mature English Pointers. PROCEDURE: Full-thickness 6 x 8-mm wounds in metatarsal and third and fourth digital pads were injected with immunostimulant or TCC at 0, 3, and 6 days after wounding. Wounds on control dogs were injected with physiologic saline solution. Using planimetric measurements at 0, 3, 6, 14, and 21 days, rates of healing were evaluated. Biopsy of the digital pad wounds at 3, 6, and 14 days was used to evaluate collagen content by hydroxyproline analysis. Biopsy specimens were also evaluated for type-I and type-III collagen, using Sirius red differential staining. RESULTS: Effect on healing rate and hydroxyproline content was best during the first week for immunostimulant. Immunostimulant- and TCC-injected wounds had more type-I collagen than did controls at 6 days; TCC-injected wounds had the most type-I collagen. At 14 days, the amount of type-I collagen in TCC-injected wounds was significantly greater than that in other wounds. CONCLUSIONS: Tested medications had positive effects on healing of pad wounds. CLINICAL RELEVANCE: Intralesional injection of medications helps ensure their presence for enhancement of wound healing. The benefit could be lost with topical use in a bandage if the bandage is lost or becomes wet.

Serum biochemical values in sled dogs before and after competing in long-distance races.

OBJECTIVE: To measure and compare blood values in sled dogs before and after long-distance racing. DESIGN: Prospective study. ANIMALS: 17 adult sled dogs in the 1991 Iditarod Trail Sled Dog Race and 21 in a simulated sled dog race. PROCEDURE: Blood samples were obtained from 17 dogs 7 days before they began and after they finished (finisher group) or were eliminated from (nonfinisher group) the Iditarod Trail Sled Dog Race. Blood samples were also obtained from 21 dogs before and after a simulated sled dog race. RESULTS: In finisher-group dogs, BUN and uric acid (UA) concentrations were increased after racing; nonfinisher-group dogs had significantly lower postrace BUN and UA concentrations. Significant increases in creatine kinase (CK) and aspartate transferase (AST) activities were detected in all dogs after racing, and postrace values were higher in nonfinisher-group dogs, compared with finisher-group dogs. Mean alkaline phosphate activities were significantly increased after racing in nonfinisher-group dogs only. In dogs that ran the simulated race, postrace values for serum albumin, total protein, calcium, and potassium concentrations, as well as Hct, hemoglobin concentration, and RBC count, were significantly lower than prerace values. Postrace values for alkaline phosphate, alanine transaminase, AST, lactate dehydrogenase, CK, BUN, and UA were significantly higher than prerace values. CLINICAL IMPLICATIONS: High CK activities are indicative of severe muscle degeneration and, in sled dogs, may represent a degree of muscle breakdown beyond which a dog cannot continue to work. Markedly high CK, and possibly AST, serum activities may be indicators of performance failure in sled dogs competing in long-distance races.

Different gradients for neurotransmitter metabolites and protein in horse cerebrospinal fluid.

The serotonin metabolite, 5-hydroxyindoleacetic acid (5-HIAA) and the dopamine metabolite, homovanillic acid (HVA) in the cerebrospinal fluid (CSF) of seven clinically normal horses were evaluated with reverse phase high pressure liquid chromatography and electrochemical detection. Comparisons of the neurotransmitter metabolite concentrations were made on CSF collected simultaneously from the atlanto-occipital and lumbosacral regions. There were significantly higher amounts of 5-HIAA and HVA in atlanto-occipital CSF than in lumbosacral CSF. Mean 5-HIAA concentrations in atlanto-occipital and lumbosacral CSF were 206.1 +/- 37.0 nmol/L and 68.5 +/- 12.6 nmol/L, respectively. The mean HVA concentration in atlanto-occipital CSF was 254.4 +/- 50.4 nmol/L. No HVA was detected in lumbosacral CSF. In contrast, significantly greater protein concentrations were present in lumbosacral CSF than in atlanto-occipital CSF. Lumbosacral and atlanto-occipital CSF contained 32.1 +/- 3.7 mg protein/dl and 25.0 +/- 1.3 mg protein/dl, respectively. Thus, between the atlanto-occipital and lumbosacral space of the horses, a rostrocaudal gradient existed for neurotransmitter metabolites and a caudorostral gradient existed for protein.

Increased plasma levels of leukotriene B4 and prostaglandin E2 in cats experimentally inoculated with feline infectious peritonitis virus.

Specific-pathogen-free kittens experimentally infected with feline infectious peritonitis virus (FIPV) subsequently demonstrated increased plasma levels of the arachidonic acid metabolites, leukotriene (LT) B4 and prostaglandin (PG) E2. Significant increases (P less than 0.025) in LTB4 plasma levels occurred in all (5/5) FIPV-inoculated kittens on postchallenge-exposure days (PCD) 7 and 14 vs PCD 0. Significant increases (P less than 0.05) in PGE2 plasma levels occurred in 80% (4/5) of FIPV-infected kittens on PCD 7 and 14. Maximal mean plasma levels of LTB4 and PGE2 occurred on PCD 7 (502.5 +/- 45.6 pg/ml and 1108.0 +/- 247.9 pg/ml, respectively). A positive correlation was found between LTB4 plasma levels and body temperature (r = 0.609, P less than 0.01). Mean survival time in FIPV-inoculated kittens was 19.4 +/- 3.2 days. Gross lesions, including peritoneal or pleural effusions (or both) and connective tissue edema, indicated an increased vascular permeability in the FIPV-infected kittens. Histologically, lesions were characterized by vasculitis or perivasculitis, vasodilatation, perivascular edema, and fibrinonecrotizing and pyogranulomatous inflammation. Immunofluorescent studies of tissues from FIPV-infected kittens demonstrated foci of polymorphonuclear leukocytes and FIPV-positive macrophages oriented around dilated blood vessels. Seemingly, arachidonic acid metabolites, including LTB4 or PGE2 released from macrophages, neutrophils or other cells, may be involved in the pathogenesis of FIP vascular and inflammatory lesions and in some of the clinical disease manifestations.

Analysis of equine cisterna magna cerebrospinal fluid for the presence of some monoamine neurotransmitters and transmitter metabolites.

Small volumes (0.05 ml) of cisterna magna cerebrospinal fluid (CSF) from 23 neurologically normal horses were analysed for the monoamine neurotransmitters dopamine, norepinephrine, epinephrine, serotonin and their metabolites using high pressure liquid chromatography and electrochemical detection. Two metabolites, homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA) were present in all CSF samples. The deaminated and methylated metabolite of dopamine, HVA, was present at a mean concentration of 42.33 +/- 3.14 ng/ml of CSF. The deaminated metabolite of serotonin, 5-HIAA, was present at a mean concentration of 45.52 +/- 3.65 ng/ml of CSF. A positive correlation was found between the CSF concentrations of HVA and 5-HIAA (r = 0.72, p = 0.0003). The mean ratio of HVA to 5-HIAA concentrations was 1.07 +/- 0.05. The ratios of HVA to 5-HIAA concentrations were found to be more indicative of the serotonergic metabolite 5-HIAA (r = -0.62, p = 0.0016) than the dopaminergic metabolite HVA (r = 0.11, p = 0.60). There was a stronger relationship between the concentrations of 5-HIAA and the ratios of HVA to 5-HIAA in male CSF (r = -0.85, p = 0.0006) than in female CSF (r = -0.54, p = 0.01). Concentrations of CSF neurotransmitter metabolites were evaluated in horses grouped by age (0-4, 5-9 and 10-13 years). The youngest group of horses had a significantly (p = 0.003) greater CSF concentration of HVA than of 5-HIAA. The 10-13-year-old horses had a significantly (p = 0.02) lower mean CSF HVA concentration than the 0-4-year-old horses. No age-related differences in CSF 5-HIAA concentrations were detected.

Analysis of cat retina for dopamine, dihydroxyphenylacetic acid, 3-methoxytyramine and homovanillic acid.

Twenty retinas from 10 cats were evaluated for dopamine (DA) and its metabolites dihydroxyphenylacetic acid (DOPAC), 3-methoxytyramine (3-MT) and homovanillic acid (HVA) by high pressure liquid chromatography and electrochemical detection. Dopamine was present in all 20 retinas at a mean concentration of 3.00 +/- 0.54 ng/mg protein. Dihydroxyphenylacetic acid, 3-MT and HVA were detected in 16, 14 and 9 retinas respectively. In retinas in which these metabolites were detectable, they were present in the following mean concentrations: DOPAC, 1.07 +/- 0.21 ng/mg protein; 3-MT, 3.44 +/- 0.97 ng/mg protein and HVA, 4.54 +/- 1.05 ng/mg protein. Significantly higher concentrations of 3-MT (p = 0.0108, paired t test) and HVA (p = 0.0166, paired t test) than DOPAC were present in cat retina. Linear correlation analysis between DA and its metabolites indicated that the 3-MT and DOPAC concentrations correlated well with each other and with the amount of DA in cat retina. The concentrations of the end product metabolite, HVA, had poor correlations with the concentrations of 3-MT, DOPAC or DA. These data indicated that once DA is released in cat retina it can be metabolized to 3-MT, DOPAC and HVA.

Determination of homovanillic acid, 5-hydroxyindoleacetic acid and pressure in the cerebrospinal fluid of collie dogs following administration of ivermectin.

Twelve adult Collie dogs were studied to determine the effects of ivermectin on neurotransmitter metabolites released from the brain into the cerebrospinal fluid (CSF) and on CSF pressure. Ten of the 12 Collies were given ivermectin orally at a concentration of 200 micrograms/kg body weight. Three of these 10 Collies showed clinical signs of ivermectin-induced toxicosis which progressed into a state of unresponsive recumbency in 2 dogs. Cerebrospinal fluid pressures and neurotransmitter metabolite concentrations in cisterna magna CSF were analysed 49 to 50 hours after administration of ivermectin in 6 of the 10 treated dogs, and in the 2 untreated control Collies. Cerebrospinal fluid pressures were within normal limits in all dogs. However, compared to the CSF concentrations in the 2 untreated and 3 non-reactive Collies, the 2 ivermectin-reactive Collies still in recumbency had elevated CSF concentrations of homovanillic acid (HVA), a metabolite of dopamine, and 5-hydroxyindoleacetic acid (5-HIAA), a metabolite of serotonin. These findings suggest an association between altered neurotransmission and severe ivermectin-induced neurological abnormalities. No evidence of elevated intracranial pressure was found.

The effects of varying dietary n-6 to n-3 fatty acid ratios on platelet reactivity, coagulation screening assays, and antithrombin III activity in dogs.

Thirty beagles were placed on diets containing ratios of n-6 to n-3 fatty acids ranging from 5:1 to 100:1 for 12 weeks to determine the effects of these diets on platelet reactivity, coagulation screening assays, and antithrombin III activity. Although small changes were observed in adenosine diphosphate (ADP)-, collagen-, and arachidonic acid-induced platelet aggregation and 14C-serotonin release, fibrinogen concentrations, and antithrombin III activities during the 12-week study, these changes were not of clinical significance and did not correlate with the varying ratios of n-6 to n-3 fatty acids.

The greyhound dog as a model for studying pressure ulcers.

Because of their angular conformation, short hair, and thin skin, greyhounds are particularly subject to development of pressure ulcers. Greyhounds, therefore, can serve as a model to study pressure ulcers, either naturally occurring pressure ulcers or induced dermal pressure lesions. A method for inducing dermal pressure lesions was developed using a short-limb walking cast on one pelvic limb of the dog. Physical characteristics, dermal thromboxane B2 concentrations, and histopathologic changes were used to determine the severity of the lesions. Different lesion severities can be induced over the calcaneal tuberosity depending upon the amount of padding in the cast and the length of time the cast is in place. The technique for inducing a mild dermal pressure lesion is described.