Antidepressant Drug-Induced Hypothalamic Cooling in Syrian Hamsters

Abstract

Antidepressant drugs have been reported to alter the circadian pattern of body temperature, but specific effects on the amplitude or on average body temperature are not consistent, and there have been no specific studies to examine chronic drug effects on brain temperature. To address these issues, hypothalamic temperature (Thy) was monitored telemetrically in hamsters treated with three antidepressant drugs: the monoamine oxidase inhibitor (MAOI), clorgyline; the 5HT reuptake inhibitor, fluoxetine; and the alkali metal, lithium. For comparison, hamsters were also treated with two neuroleptic drugs, chlorpromazine and haloperidol. Each of the three antidepressant drugs, but neither of the neuroleptic drugs, produced a chronic decrease in diurnal (rest-phase) hypothalamic temperature. The Thy-decreasing effect of clorgyline was not prevented by pinealectomy, and Thy decreased more than peritoneal temperature (Tp), thus reducing the temperature difference between the hypothalamus and the peritoneal cavity. Less general effects of the antidepressants were also observed. Clorgyline and fluoxetine, but not lithium, delayed the 24-hour rhythm of Thy. Clorgyline and lithium, but not fluoxetine decreased the average 24-hour Thy. The neuroleptics chlorpromazine and haloperidol decreased the amplitude of the 24-hour Thy rhythm. The fact that chronic antidepressant drugs, but not neuroleptic drugs, decrease Thy is consistent with their different neurotransmitter effects and clinical applications, and raises the possibility that their antidepressant property might be related to their capacity to decrease Thy during sleep.

Simultaneous Measurement of Brain and Core Temperature in the Rat during Fever, Hyperthermia, Hypothermia and Sleep

“…If too close to the surface of the animal, lower temperature readings will be the result [16]. If implanted deeper, however, the temperature readout of the brain, for example, is commonly higher than that of the deep core [1,2]. This can be both an advantage and a disadvantage.…”

“…The resulting, often large hematomas in the brain complicate recovery of the animals after surgery. Also, concomitant monitoring of brain and core temperatures may be more complicated (with interfering radiofrequencies), although this has been done [2]. Another drawback to this method is the fact that the length of the metal rod greatly decreases the number of sites enabling temperature measurements in the brain.…”

“…Another, relatively new method for monitoring brain temperature has been developed by Minimitter [2,17,18]. In short, it is based on radiotelemetry, where a radiotransmitter, which is connected to a temperature-measuring metal rod, is cemented to the skull of the animal.…”

“…The reasons for this are the following: it needs to be established whether brain and core temperatures are similar during fever (elevated set point temperature), hyperthermia (elevated body temperature), hypothermia (low body temperature) and sleep (decreased set point); all these thermal states are relevant to patients suffering from insults to the CNS, and receiving medication to minimize neural damage. Also, studies in both humans [1] and animals [2] have confirmed that the core and the brain temperatures do not always concur with one another. This paper describes an animal model (the rat) in which we have developed a method to measure brain and core temperatures concomitantly.…”

Inhibition of the human two‐pore domain potassium channel, TREK‐1, by fluoxetine and its metabolite norfluoxetine

“…It is possible, however, that block of TREK-1 channels may contribute to the antidepressant action of this drug. Antidepressant drugs have been reported to decrease hypothalamic temperature and it has been suggested that this function, during sleep, may contribute to the antidepressant action of at least some of these agents (Duncan et al, 1995). Since TREK-1 is a heat-activated channel, which is highly expressed in the hypothalamus (Maingret et al, 2000a), it is possible that fluoxetine block of TREK-1 contributes to its antidepressant action.…”