What's a brain: neuroanatomy and neurochemistry of anxiety disorders in dogs

This review deals with the neurocircuitry of fear and anxiety disorders, with the focus on neuroanatomy and neurochemistry. This knowledge is required to correctly diagnose and treat dogs with anxiety-related behavioral disorders. Research to date has shown the involvement of the frontal cortex, the amygdala, the thalamus and the hippocampus as core regions in regulating fear. Imbalances (hyper- or hypoactivation) in this fear circuitry can trigger inappropriate fear responses, i.e. anxiety disorders. Serotonin, dopamine and norepinephrine are the main neurotransmitters of emotion in the brain, but gamma-aminobutyric acid (GABA), glutamate, and the hypothalamic-pituitary-adrenal (HPA) axis producing glucocorticoids are also important in the neurochemistry of anxiety

Functional brain imaging : a brief overview of imaging techniques and their use in human and canine anxiety research

When used in combination with specific radioactive markers, functional imaging modalities such as Single Photon Emission Computed Tomography (SPECT) and Positron Emission Tomography (PET) enable the visualization of several neurotransmitter receptors and transporters, as well as of the perfusion and metabolism of the brain. This paper gives an overview of the functional imaging techniques, as well as of the studies that have been performed on humans and canines with anxiety disorders. Thus far, most of the research in this field has been focused on brain perfusion and the serotonergic and dopaminergic neurotransmitters, and less on gamma-aminobutyric acid (GABA), glutamate, norepinephrine and the hypothalamic-pituitary-adrenal (HPA) axis

Nuclear medicine: investigation of renal function in small animal medicine

Kidney function investigations in veterinary medicine are traditionally based on blood analysis (blood urea nitrogen (BUN) and serum creatinine concentration) and / or urinalysis (urine specific gravity, protein-to-creatinine ratio or fractional excretion). Morphologic information is usually obtained by abdominal radiography or ultrasonography. However, when more specific information on the functionality of the kidneys is needed, nuclear medicine offers various tracers that specifically represent glomerular filtration rate, effective renal plasma flow or functional renal mass, sometimes combining functional and morphologic data. These procedures can be based on blood sampling techniques (non-imaging methods), or data can be obtained using a gamma-camera (imaging methods). The most commonly used radionuclides for the examination of kidney function in small animal medicine are discussed in this review

Evaluation of feline renal perfusion with contrast-enhanced ultrasonography and scintigraphy

Contrast-enhanced ultrasound (CEUS) is an emerging technique to evaluate tissue perfusion. Promising results have been obtained in the evaluation of renal perfusion in health and disease, both in human and veterinary medicine. Renal scintigraphy using Tc-99m-Mercaptoacetyltriglycine (MAG(3)) is another non-invasive technique that can be used to evaluate renal perfusion. However, no data are available on the ability of CEUS or Tc-99m-MAG(3) scintigraphy to detect small changes in renal perfusion in cats. Therefore, both techniques were applied in a normal feline population to evaluate detection possibilities of perfusion changes by angiotensin II (AT II). Contrast-enhanced ultrasound using a bolus injection of commercially available contrast agent and renal scintigraphy using Tc-99m-MAG(3) were performed in 11 healthy cats after infusion of 0,9% NaCl (control) and AT II. Angiotensin II induced changes were noticed on several CEUS parameters. Mean peak enhancement, wash-in perfusion index and wash-out rate for the entire kidney decreased significantly after AT II infusion. Moreover, a tendency towards a lower wash-in area-under-the curve was present. Renal scintigraphy could not detect perfusion changes induced by AT II. This study shows that CEUS is able to detect changes in feline renal perfusion induced by AT II infusion

PET quantification of [18F]MPPF in the canine brain using blood input and reference tissue modelling

Numerous studies have shown that the serotonin(1A) (5-HT1A) receptor is implicated in the pathophysiology and treatment of several psychiatric and neurological disorders. Furthermore, functional imaging studies in a variety of species have demonstrated that 4-(2'-Methoxyphenyl)-1-[2'-(N-2 ''-pyridinyl)-p-[F-18]fluorobenzamidoethylpiperazine ([F-18]MPPF) is a valid and useful PET tracer to visualize the 5HT(1A) receptor. However, to our knowledge, [F-18] MPPF has never been demonstrated in the canine brain. The ability to image the 5HT(1A) receptor with PET in dogs could improve diagnosis and therapy in both canine and human behavioural and neuropsychiatric disorders. To examine the potential use of [F-18]MPPF in dogs, five healthy adult laboratory beagles underwent a 60-minutes dynamic PET scan with [F-18]MPPF while arterial blood samples were taken. For each region of interest, total distribution volume (V-T) and corresponding binding potential (BPND) were calculated using the 1-tissue compartment model (1-TC), 2-Tissue compartment model (2-TC) and Logan plot. The preferred model was chosen based on the goodness-of-fit, calculated with the Akaike information criterium (AIC). Subsequently, the BPND values of the preferred compartment model were compared with the estimated BPND values using three reference tissue models (RTMs): the 2-step simplified reference tissue model (SRTM2), the 2-parameter multilinear reference tissue model (MRTM2) and the Logan reference tissue model. According to the lower AIC values of the 2-TC model compared to the 1-TC in all ROIs, the 2-TC model showed a better fit. Calculating BPND using reference tissue modelling demonstrated high correlation with the BPND obtained by metabolite corrected plasma input 2-TC. This first-indog study indicates the results of a bolus injection with [F-18] MPPF in dogs are consistent with the observations presented in the literature for other animal species and humans. Furthermore, for future experiments, compartmental modelling using invasive blood sampling could be replaced by RTMs, using the cerebellum as reference region

Estimation of the optimal dosing regimen of escitalopram in dogs : a dose occupancy study with [11C]DASB

Although the favourable characteristics of escitalopram as being the most selective serotonin reuptake inhibitor and having an increased therapeutic efficacy via binding on an additional allosteric binding site of the serotonin transporter, its dosing regimen has not yet been optimized for its use in dogs. This study aimed to estimate the optimal dosing frequency and the required dose for achieving 80% occupancy of the serotonin transporters in the basal ganglia. The dosing frequency was investigated by determining the elimination half-life after a four day oral pre-treatment period with 0.83 mg/kg escitalopram (3 administrations/day) and a subsequent i. v. injection 0.83 mg/ kg. Blood samples were taken up to 12 hours after i. v. injection and the concentration of escitalopram in plasma was analysed via LC-MSMS. The dose-occupancy relationship was then determined by performing two PET scans in five adult beagles: a baseline PET scan and a second scan after steady state conditions were achieved following oral treatment with a specific dose of escitalopram ranging from 0.5 to 2.5 mg/kg/day. As the elimination half-life was determined to be 6.7 hours a dosing frequency of three administrations a day was proposed for the second part of the study. Further it was opted for a treatment period of four days, which well exceeded the minimum period to achieve steady state conditions. The optimal dosing regimen to achieve 80% occupancy in the basal ganglia and elicit a therapeutic effect, was calculated to be 1.85 mg/kg/day, divided over three administrations. Under several circumstances, such as insufficient response to other SSRIs, concurrent drug intake or in research studies focused on SERT, the use of escitalopram can be preferred over the use of the already for veterinary use registered fluoxetine, however, in case of long-term treatment with escitalopram, regularly cardiac screening is recommended