Role of 5‐hydroxytryptamine in ketamine‐induced hypothermia in the rat

Abstract

Summary1. Intraperitoneal injection of graded doses of ketamine produced a dosedependent fall in body temperature of rats. Similarly, intracerebral injection of much smaller doses produced hypothermia. 2. Pretreatment of the rats with p-chlorophenylalanine (PCPA) greatly attenuated the hypothermic response to ketamine whereas the intraperitoneal injection of 5-hydroxytryptophan in PCPA-treated rats restored the hypothermic effect of ketamine. 3. Depletion of the brain monoamines by reserpine completely prevented the ketamine-induced hypothermia. Treatment with sodium diethyldithiocarbamate (DEDTC), however, did not modify the hypothermic effect of ketamine. 4. Pretreatment of the rats with pargyline potentiated the ketamine-induced hypothermia. 5. Depletion of brain monoamines by reserpine in combination with inhibition of noradrenaline biosynthesis (DEDTC) resulted in a long lasting fall in temperature which was not modified by ketamine. 6. When the ambient temperature was raised from 260 C to 320 C, ketamineinduced hypothermia was much reduced and superimposed on a hyperthermia which occurred in all animals. 7. It is concluded that ketamine produces hypothermia in rats possibly through the release of 5-hydroxytryptamine in the hypothalamus and that this effect is similar in some respects to that produced by morphine in non-tolerant rats.

The serotonin 2C receptor agonist WAY-163909 attenuates ketamine-induced hypothermia in mice

“…Consistent with many previous studies, we found in that ketamine dose-dependently induces hypothermia (Fahim et al, 1973; Garami et al, 2017; Schmitz et al, 2016). Furthermore, we found that mice do not become tolerant to this effect of ketamine over the course of three injections spaced at once per week.…”

“…These findings led us to the hypothesis that the activation of 5-HT 2 receptors may attenuate AIH. In the present study, we use the injectable anesthetic ketamine to assess this hypothesis because 1) its dosing can be readily controlled because it is injected rather than inhaled, 2) it is well known to induce dose-dependent hypothermia in several species (Fahim et al, 1973; Garami et al, 2017; Schmitz et al, 2016), and the role of serotonin and specific serotonin receptors in ketamine-induced hypothermia remains controversial (Fahim et al, 1973). However, it is important to note that the use of ketamine as an anesthetic in humans is limited to specific cases such as hemorrhagic shock, hemodynamic instability, and bronchodilation (Kurdi et al, 2014), in contrast to its more extensive use as a veterinary anesthetic.…”

Impact of repeated anesthesia with ketamine and xylazine on the well-being of C57BL/6JRj mice

“…2 h after lights turned on). It should be noted that both substances, ketamine and xylazine, evoke hypothermia in rodents [ 57 , 58 ], which in turn triggers building of high and complex nests to decrease the amount of radiated heat and, thus, alleviate thermal discomfort [ 59 ]. In our previous study, we found that neither single nor repeated anesthesia with isoflurane impaired nest scores [ 4 ] obtained by using the same nesting protocol [ 56 ].…”

Somatic influences on subjective well-being and affective disorders: the convergence of thermosensory and central serotonergic systems

“…Interestingly, activations of the medial orbitofrontal cortex and ventral striatum were associated with improvements of overall depression scores as measured by the MADRS scores, while activation of the dorsal anterior cingulate cortex, extending into the pregenual cingulate/callosal region was associated specifically with the anti-anhedonia effects of ketamine, as measured using the Snaith-Hamilton pleasure scale (SHAPS), The SHAPS is a validated 14-item, self-administered scale that measures levels of anticipatory anhedonia (Leventhal et al, 2006 ; Franken et al, 2007 ; Nakonezny et al, 2010 ). Interestingly, the ability of ketamine to induce thermoregulatory cooling in animals (Fahim et al, 1973 ; Pietersen et al, 2006 ), resulting in reduced core body temperature, was a primary consideration in selection of ketamine for initial clinical studies for the off-label use of ketamine for treatment of children with pediatric bipolar disorder/fear of harm phenotype (Papolos et al, 2013 ), who appear to suffer from an inability to dissipate heat (Papolos et al, 2009 ). These findings suggest that WBH and ketamine, which both have strong thermoregulatory cooling effects, may activate the same positive affective or anti-anhedonic circuits, and that activation of these circuits, particularly the dorsal anterior cingulate cortex/pregenual cingulate cortex, may play a role in the anti-anhedonic effects.…”