Changes in extracellular serotonin in rat hypothalamus  affect thermoregulatory function

Lin, Mao Tsun; Tsay, Huey Jen; Su, Wen-Hong; Chueh, Fu-Yu

doi:10.1152/ajpregu.1998.274.5.r1260

Cited by 72 publications

(90 citation statements)

References 41 publications

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“…Hypothermia was mediated by many types of receptors including serotonergic 5-HT 1A (Hillegaart, 1991;Millan et al, 1993;Lin et al, 1998), 5-HT 7 (Guscott et al, 2003;Faure et al, 2006), dopaminergic D 2 (Oerther, 2000) and adrenergic α 2 receptors (Feleder et al, 2004). It appears that both 5-HT 1A and 5-HT 7 receptors exerted a small tonic inhibition on T cor , consistent with the role of those binding sites in thermoregulation (Lin et al, 1998). Using the selective 5-HT 7 receptor antagonist SB-639970 we ruled out a possible involvement of 5-HT 7 receptors in hypothermia under our experimental condition.…”

Section: Discussionmentioning

confidence: 99%

“…Thus behavioral signs and symptoms can be mild, moderate or severe (Boyer and Shannon, 2005). Changes in body-core temperature (claudqcT cor ), attributable to 5-HT-mediated thermoregulation in the central nervous system (Lin et al, 1998), are a most obvious indication for the toxidrome (Isbister and Buckley, 2005). Several studies conducted in animals have revealed both hyperthermia and hypothermia in the toxidrome (Abdel-Fattah et al, 1995, 1997Nisijima et al, 2001Nisijima et al, , 2003.…”

Section: Introductionmentioning

confidence: 99%

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Characterization of serotonin-toxicity syndrome (toxidrome) elicited by 5-hydroxy-l-tryptophan in clorgyline-pretreated rats

Ma¹,

Zhang²,

Jenney³

et al. 2008

European Journal of Pharmacology

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Patients are at high risk of developing serotonin-toxicity syndrome (toxidrome) when they take multiple serotonergic drugs, particularly co-administered with monoamine oxidase inhibitors or 5-hydroxytryptamine (5-HT) reuptake blockers. The toxidrome can vary from mild to severe. The primary goal of the present study was to understand the relationship between behavioral signs and degrees of toxidrome induced by 5-hydroxy-L-tryptophan (5-HTP) in clorgylinized rats. The severity was obtained by scoring behavioral signs including head shakes, penile erection, forepaw treading, hind limb abduction, Straub tail and tremor. It was found that 5-HTP produced a dosedependent increase in degrees of the toxidrome. Furthermore, correlation between the toxidrome and changes in body-core temperature (claudqcT cor ) was determined. There was hypothermia in the mild toxidrome (claudqcT cor < −1 °C), high hyperthermia in the severe toxidrome (claudqcT cor > +2 °C) and a small change in T cor in the moderate toxidrome (−1 °C < claudqcT cor < +2 °C). Thus, claudqcT cor in response to drugs can be used to estimate the severity of the toxidrome. The second attempt was to identify the receptors mediating those changes. 5-HT 1A receptors were involved in the hypothermic response while 5-HT 2A and NMDA receptors mediated head shakes, hyperthermia, forepaw treading and Straub tail. Lastly, antidotal effect of cyproheptadine and (+)-MK-801 was examined. Both drugs blocked hyperthermia and death. However, the effects on mortality became poor when the antidotes were injected 60 min after high hyperthermia had been induced. These findings demonstrate the importance of the time frame using antidotes in the treatment of the 5-HT toxidrome.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Characterization of serotonin-toxicity syndrome (toxidrome) elicited by 5-hydroxy-l-tryptophan in clorgyline-pretreated rats

Ma¹,

Zhang²,

Jenney³

et al. 2008

European Journal of Pharmacology

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“…Fluoxetine can induce hyperthermia in rats (Lin et al, 1998). The activity of PLA 2 as well that of other enzymes might be expected to increase with an increase in temperature .…”

Section: Saline Control Fluoxetinementioning

confidence: 98%

Imaging Brain Phospholipase A2-Mediated Signal Transduction in Response to Acute Fluoxetine Administration in Unanesthetized Rats

Chang

Klaff

et al. 2003

Neuropsychopharmacol

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Fluoxetine, a selective serotonin (5-hydroxytryptamine, 5-HT) reuptake inhibitor, is used widely to treat depression and related disorders. By inhibiting presynaptic 5-HT reuptake, fluoxetine is thought to act by increasing 5-HT in the synaptic cleft, thus 5-HT binding to postsynaptic 5-HT 2A/2C receptors. These receptors can be coupled via a G-protein to phospholipase A 2 (PLA 2 ), which when activated releases the second messenger arachidonic acid from synaptic membrane phospholipids. To image this activation, fluoxetine (10 mg/kg) or saline vehicle was administered i.p. to unanesthetized rats, and regional brain incorporation coefficients k* of intravenously injected radiolabeled arachidonic acid were measured after 30 min. Compared with vehicle, fluoxetine significantly increased k* in prefrontal, motor, somatosensory, and olfactory cortex, as well as in the basal ganglia, hippocampus, and thalamus. Many of these regions demonstrate high densities of the serotonin reuptake transporter and of 5-HT 2A/2C receptors. Brain stem, spinal cord, and cerebellum, which showed no significant response to fluoxetine, have low densities of the transporters and receptors. The results show that it is possible to image quantitatively PLA 2 -mediated signal transduction in vivo in response to fluoxetine.

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“…It has been described that local perfusion of the hypothalamus with 5-hydroxytryptophan (a 5-HT precursor) or fluoxetine (a 5-HT reuptake inhibitor) increases body temperature by increasing extracellular concentrations of 5-HT, which activate central 5-HT 2A receptors [20,21], although activation of these receptors in the peripheral system leads to hypothermia [22]. Additionally, an activation of 5-HT 1A receptors in the hypothalamus leads to hypothermia [23].…”

Section: Discussionmentioning

confidence: 99%

Serotonin is involved in the psychostimulant and hypothermic effect of 4-methylamphetamine in rats

Rubio

López-Arnau

Piccoli

et al. 2015

Neuroscience Letters

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Abstract4-methylamphetamine (4-MA) has recently emerged as a designer drug of abuse in Europe and it is consumed always with amphetamine. There have been reported some deaths and non-fatal intoxications related to 4-MA. We investigated the changes in locomotor activity and body temperature after 4-MA administration to male SpragueDawley rats. Our experiments were carried out at a normal or high ambient temperature. 4-MA (2.5 -10 mg/Kg, given subcutaneously) increased, in a dosedependent manner, the horizontal locomotor activity that was significantly reduced by ketanserin, p-cholorophenylalanine (pCPA) or haloperidol. In addition, we have studied the effect of 4-MA on core body temperature by means of an implanted electronic thermograph, enabling continuous measurement of body temperature. We observed a dose-dependent hypothermic response to 4-MA that reached a maximum 45 min after a single injection. We also evidenced slight tachyphylaxis to the hypothermic effect when 4-MA was administered four times in a 2 h interval. The pre-treatment of animals with pCPA or pindolol, but not with ketanserin, fully abolished the hypothermic effect of 4-MA. With all that, we conclude that hypothermia induced by 4-MA is due to the release of 5-HT which activates postsynaptic 5-HT 1A receptors.

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Changes in extracellular serotonin in rat hypothalamus affect thermoregulatory function

Cited by 72 publications

References 41 publications

Characterization of serotonin-toxicity syndrome (toxidrome) elicited by 5-hydroxy-l-tryptophan in clorgyline-pretreated rats

Characterization of serotonin-toxicity syndrome (toxidrome) elicited by 5-hydroxy-l-tryptophan in clorgyline-pretreated rats

Imaging Brain Phospholipase A2-Mediated Signal Transduction in Response to Acute Fluoxetine Administration in Unanesthetized Rats

Serotonin is involved in the psychostimulant and hypothermic effect of 4-methylamphetamine in rats

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