Regional Cerebral Blood Flow Changes in Dogs with Anxiety Disorders, Measured with SPECT

Vermeire, Simon; Audenaert, Kurt; Dobbeleir, André; Meester, Rudy De; Vandermeulen, Eva; Waelbers, Tim; Peremans, Kathelijne

doi:10.1007/s11682-009-9076-1

Cited by 29 publications

(22 citation statements)

References 45 publications

(51 reference statements)

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“…Moreover, recently, the US Food and Drug Administration approved S-ketamine nasal spray as an new therapy for treatment resistant depression. Since anxiety disorders in dogs show several similarities with human mood disorders [17][18][19][20][21][22][23], intranasal ketamine could also be a valuable alternative treatment for certain canine behavioural disorders. Brain imaging studies have reported similar abnormalities in regional cerebral blood flow of certain brain regions in dogs with pathological anxiety and in humans suffering from depression and anxiety disorders [17][18][19][20][21][22][23].…”

Section: Introductionmentioning

confidence: 99%

“…Since anxiety disorders in dogs show several similarities with human mood disorders [17][18][19][20][21][22][23], intranasal ketamine could also be a valuable alternative treatment for certain canine behavioural disorders. Brain imaging studies have reported similar abnormalities in regional cerebral blood flow of certain brain regions in dogs with pathological anxiety and in humans suffering from depression and anxiety disorders [17][18][19][20][21][22][23]. Furthermore, altered perfusion of these brain regions following intravenous subanesthetic ketamine administration has been demonstrated both in humans and dogs [24][25][26][27][28][29][30].…”

Section: Introductionmentioning

confidence: 99%

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Pharmacokinetics, absolute bioavailability and tolerability of ketamine after intranasal administration to dexmedetomidine sedated dogs

et al. 2020

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Intranasal ketamine has recently gained interest in human medicine, not only for its sedative, anaesthetic or analgesic properties, but also in the management of treatment resistant depression, where it has been shown to be an effective, fast acting alternative treatment. Since several similarities are reported between human psychiatric disorders and canine anxiety disorders, intranasal ketamine could serve as an alternative treatment for anxiety disordered dogs. However, to the authors knowledge, intranasal administration of ketamine and its pharmacokinetics have never been described in dogs. Therefore, this study aimed to examine the pharmacokinetics, absolute bioavailability and tolerability of intranasal ketamine administration compared with intravenous administration. Seven healthy, adult laboratory Beagle dogs were included in this randomized crossover study. The dogs received 2 mg/kg body weight ketamine intravenously (IV) or intranasally (IN), with a two-week washout period. Prior to ketamine administration, dogs were sedated intramuscularly with dexmedetomidine. Venous blood samples were collected at fixed times until 480 min post-administration and ketamine plasma concentrations were determined by liquid chromatographytandem mass spectrometry. Cardiovascular parameters and sedation scores were recorded at the same time points. Non-compartmental pharmacokinetic analysis revealed a rapid (Tmax = 0.25 ± 0.14 h) and complete IN bioavailability (F = 147.65 ± 49.97%). Elimination half-life was similar between both administration routes (T1/2el IV = 1.47 ± 0.24 h, T1/2el IN = 1.50 ± 0.97 h). Heart rate and sedation scores were significantly higher at 5 and 10 min following IV administration compared to IN administration, but not at the later time-points.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Pharmacokinetics, absolute bioavailability and tolerability of ketamine after intranasal administration to dexmedetomidine sedated dogs

et al. 2020

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“…Moreover, this study obtained a comparable increase in rCBF of the left frontal cortex (2–3%) as Catafau et al (2001) reported in 7 depressed patients (medication-resistant). Although we did not assess behavioural measurements, this observed perfusion increase might initiate speculation on the potential role of rTMS in behaviour-disordered dogs, especially in anxiety disordered animals that have been reported to suffer from hypoperfusion in the left frontal cortex [ 35 ]. Similarly, increased rCBF in the left frontal region after HF-rTMS has been associated with clinical improvement in MDD patients [ 51 ].…”

Section: Discussionmentioning

confidence: 99%

Anaesthesia, not number of sessions, influences the magnitude and duration of an aHF-rTMS in dogs

et al. 2017

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BackgroundCurrently, the rat has been a useful animal model in brain stimulation research. Nevertheless, extrapolating results from rodent repetitive Transcranial Magnetic Stimulation (rTMS) research to humans contains several hurdles. This suggests the desperate need for a large animal model in translational rTMS research. The dog would be a valid choice, not only due to the fact that humans and dogs share a neurophysiological background, but a similar neuropathological background as well.HypothesisIn order to evaluate the feasibility of the canine rTMS animal model, this study aimed to evaluate the neurophysiological response in dogs on a, clinically used, accelerated high frequency (aHF) rTMS protocol. This aHF-rTMS (20 Hz) protocol was performed under anaesthesia or sedation and either 20 sessions or 5 sessions were given to each dog.Methods21 healthy dogs were randomly subjected to one of the four aHF-rTMS protocols (1 sham and 3 active protocols). For each dog, the perfusion indices (PI), of a [99mTc]HMPAO scan at 4 time points, for the left frontal cortex (stimulation target) were calculated for each protocol.ResultsConcerning sham stimulation, the average PI remained at the baseline level. The main result was the presence of a direct transitory increase in rCBF at the stimulation site, both under anaesthesia and sedation. Nevertheless the measured increase in rCBF was higher but shorter duration under sedation. The magnitude of this increase was not influenced by number of sessions. No changes in rCBF were found in remote brain regions.ConclusionThis study shows that, despite the influence of anaesthesia and sedation, comparable and clinically relevant effects on the rCBF can be obtained in dogs. Since less methodological hurdles have to be overcome and comparable results can be obtained, it would be acceptable to put the dog forward as an alternative translational rTMS animal model.

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“…Images were then processed using iterative reconstruction and a Butterworth filter (cut-off 1.6 cycli/cm, order 10, ten iterations, eight subsets). Pixel size was 1.72 mm [ 24 ] .…”

Section: Methodsmentioning

confidence: 99%

The influence of subanaesthetic ketamine on regional cerebral blood flow in healthy dogs measured with 99mTc-HMPAO SPECT

et al. 2018

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Subanaesthetic ketamine has recently been proven to be a highly effective and fast acting alternative treatment for several psychiatric disorders. The mechanisms responsible for ketamine’s antidepressant effects remain unclear, but a possible explanation could be that ketamine interacts with regional cerebral blood flow (rCBF). Therefore, the effects of two subanaesthetic ketamine doses on rCBF were evaluated. Twelve dogs were randomly assigned to one of the three treatment conditions (condition saline, condition 0.5 mg/kg ketamine or condition 2 mg/kg ketamine) and received in total five saline or ketamine infusions, with one week interval. Single Photon Emission Computed Tomography (SPECT) scans with the radiotracer 99mTc-hexamethylpropylene amine oxime were performed before the start of the infusions (baseline) and 24 hours after the first (single) and last (multiple) infusion. After a wash out period of 3 months, the animals were again assigned to one of the three treatment conditions described above and the infusion/scan protocol was repeated. During the infusions, cardiovascular parameters were evaluated every ten minutes. A one-way repeated measure ANOVA was set up to assess perfusion index for each ketamine dose for the left frontal cortex (alpha = 0.05). The remaining 11 brain regions were post hoc assessed. Perfusion index was significantly increased in the left frontal cortex and in the thalamus 24 hours after single and multiple ketamine infusions compared to baseline in the 2 mg/kg condition. No clinically relevant cardiovascular effects were observed during the ketamine infusions. This study shows that subanaesthetic ketamine can increase neuronal perfusion and therefore alter neuronal function in brain regions involved in depression and anxiety disorders. These perfusion increases may possibly contribute to ketamine’s beneficial effects in these psychiatric disorders.

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Regional Cerebral Blood Flow Changes in Dogs with Anxiety Disorders, Measured with SPECT

Cited by 29 publications

References 45 publications

Pharmacokinetics, absolute bioavailability and tolerability of ketamine after intranasal administration to dexmedetomidine sedated dogs

Pharmacokinetics, absolute bioavailability and tolerability of ketamine after intranasal administration to dexmedetomidine sedated dogs

Anaesthesia, not number of sessions, influences the magnitude and duration of an aHF-rTMS in dogs

The influence of subanaesthetic ketamine on regional cerebral blood flow in healthy dogs measured with 99mTc-HMPAO SPECT

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