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

Abstract

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.

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

“…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]. Additionally, functional imaging studies have demonstrated altered function of the serotonergic system in several cortical brain regions, both in humans and dogs suffering from mood and anxiety disorders [31][32][33].…”