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J Appl Physiol 99: 1397-1401, 2005. First published May 26, 2005; doi:10.1152/japplphysiol.00435.2005
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Acute dopamine/norepinephrine reuptake inhibition increases brain and core temperature in rats

Hiroshi Hasegawa,1,2,4 Romain Meeusen,1 Sophie Sarre,2 Marc Diltoer,2 Maria Francesca Piacentini,1,3 and Yvette Michotte2

1Department of Human Physiology and Sportsmedicine, and 2Experimental Pharmacology Research Group, Department of Pharmaceutical Chemistry and Drug Analysis, Vrije Universiteit Brussel, Brussels, Belgium; 3Department of Human Movement and Sport Sciences, Istituto Universitario di Scienze Motorie, Rome, Italy; and 4Laboratory of Exercise Physiology, Faculty of Integrated Arts and Sciences, Hiroshima University, Kagamiyama, Higashihiroshima, Japan

Submitted 18 April 2005 ; accepted in final form 24 May 2005


   ABSTRACT
TOP
 ABSTRACT
MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 GRANTS
 ACKNOWLEDGMENTS
 REFERENCES
 
The purpose of the present study was to examine the effects of an acute dose of the dual dopamine (DA) and norepinephrine (NE) reuptake inhibitor bupropion (Bup) on brain (Tbrain), body core (Tcore), and tail skin (Ttail) temperature in freely moving rats and to simultaneously monitor the extracellular neurotransmitter concentrations in the preoptic area and anterior hypothalamus (PO/AH). A microdialysis probe was inserted in the PO/AH, and samples for NE, DA, and serotonin (5-HT) were collected every 20 min before and after the injection of 17 mg/kg of Bup, for a total sampling time of 180 min. Tcore was monitored using a biotelemetry system. Tbrain and Ttail, an index of heat loss response, were also measured. Both NE and DA levels in the PO/AH significantly increased after Bup injection compared with the baseline levels, reaching ~450 and 230%, respectively, 40 min after injection. There was no effect on 5-HT release. The neurotransmitter changes were accompanied by a significant decrease in Ttail and an increase in both Tbrain and Tcore compared with the baseline levels. The present results demonstrate that inhibition of NE and DA reuptake suppresses heat loss mechanisms and elevates Tbrain and Tcore in freely moving rats.

microdialysis; monoamines; preoptic area and anterior hypothalamus; body temperature

BRAIN CATECHOLAMINES ARE CONSIDERED to be involved in thermoregulation, especially in the preoptic area and anterior hypothalamus (PO/AH), which are the primary loci for maintenance of body temperature (2). A number of studies have investigated the relationship between dopamine (DA), norepinephrine (NE), and thermoregulation in the PO/AH (4, 7, 9, 32).

Our laboratory has recently shown that inhibition of PO/AH neurons by perfusion of tetrodotoxin (TTX) during exercise induces an additional increase in body core temperature (Tcore) with not only an enhancement of heat production responses but also an inhibition of heat loss mechanisms (10). The TTX-induced hyperthermia was not accompanied with any reduction in exercise behavior. Furthermore, our laboratory recently showed in a human study that central manipulation of the DA and NE system significantly influenced time trial performance, leading to a significantly higher Tcore (37). It is possible that this manipulation may enable an individual to dampen or override inhibitory signals arising from central nervous system (CNS) to cease exercise due to hyperthermia. This response appeared to occur without any change in the subjects' perceived exertion or thermal sensation and may potentially increase the risk of developing heat illness (37). Therefore, it is interesting to examine the role of these neurotransmitter systems on thermoregulatory mechanisms.

Bupropion (Bup) is a dual dopaminergic and noradrenergic reuptake inhibitor, presenting weak but relatively selective inhibition characteristics of DA reuptake. Its potency as an inhibitor of NE reuptake is one-half of that of DA, and it shows little affinity for the serotonergic transport system (1). Piacentini et al. (26) have reported an increase in hippocampal NE and DA concentrations after Bup injection and a significant decrease in peripheral prolactin concentrations using brain microdialysis and catheterization methods. These results suggest that Bup influenced neurotransmission both at the central and at the peripheral level. However, they did not address how Bup influences thermoregulatory functions. While Bup has been reported to possess thermogenic properties (15, 16) possibly relating to its amphetamine-like structure (20), no studies have examined the hypothalamic catecholamine levels, brain temperature (Tbrain) and Tcore after Bup injection.

Therefore, the purpose of the present study was to investigate the effects of an acute dose of Bup on thermoregulatory responses and the extracellular NE, DA, and serotonin (5-HT) concentrations via in vivo microdialysis and biotelemetry methods in freely moving rats with special focus on the PO/AH, which is the most important control center of thermoregulation. Because of the well-documented effects of 5-HT on the regulation of a number of physiological functions and behaviors such as sleep, fatigue, pain, arousal, and thermoregulation (11, 14), we have also investigated 5-HT concentrations in the PO/AH.


   MATERIALS AND METHODS
TOP
 ABSTRACT
 MATERIALS AND METHODS
RESULTS
 DISCUSSION
 GRANTS
 ACKNOWLEDGMENTS
 REFERENCES
 
Animal treatment.   Wistar male rats (300–350 g) were used in all experiments. Animals were housed in a room of normal ambient temperature, on a 12:12-h light-dark cycle (lights on at 0800). Animals had a standard diet with free access to food and water throughout the experiments. The procedures used in this study were carried out according to the European Guidelines on Animal Experimentation and were approved by the Ethic Committee of the Faculty of Medicine and Pharmacy of the Vrije Universiteit of Brussel.

Surgery.   Animals were anesthetized with pentobarbital sodium (60 mg/kg ip). A telemetry device (model TA10TA-F20, Data Sciences International, St. Paul, MN) was implanted in the peritoneal cavity (9). After a 6-day recovery period, rats were anesthetized with pentobarbital sodium (60 mg/kg ip) and placed on a stereotaxic frame. The skull was exposed, and two intracerebral guides (model MAB 6.14.IC, Microbiotech, Stockholm, Sweden) were implanted. One guide was inserted in the left PO/AH (anterior: –0.3 mm, lateral: –0.8 mm, ventral: +6.7 mm, relative to bregma) for the microdialysis probe, and one in the right frontal cortex (anterior: +2.5 mm, lateral: +3.2 mm, ventral: +2.0 mm, relative to bregma) for the thermocouple probe to measure brain temperature (23). The cannulas were secured to the skull using dental cement (Durelon, Espe, Germany). Postoperative analgesia was provided to each rat by giving a single injection of ketofen (4 mg/kg ip). Microdialysis experiments were carried out 48 h after implantation of the probes.

Experimental producers.   On the day of experiment, rats were anesthetized with 4% sevoflurane and oxygen insufflated into a transparent chamber. After induction, the rat was maintained under anesthesia to change the probes, using 1.5% sevoflurane delivered with oxygen at 0.8 l/min via a facemask (35). The guides were replaced by a microdialysis probe with a membrane length of 2 mm (model MAB 6.14.2, Microbiotech, Stockholm, Sweden) and a thermocouple probe in the prefrontal cortex (HYP-O-SLE, Omega, Stamford, CT). The thermocouple for tail skin temperature (Ttail) was also attached with tape on the dorsal surface of the skin ~10 mm from the base of the tail.

The microdialysis probes were connected to a microinfusion pump (model CMA 100, CMA Microdialysis, Stockholm, Sweden) and were perfused with Ringer solution (147 mM NaCl, 4 mM KCl, and 2.3 mM CaCl2) at a flow rate of 1 µl/min. Microdialysis sampling was started after 2 h of probe implantation. Then, after 2 h of baseline collections, rats randomly received either an intraperitoneal injection of 17 mg/kg of Bup hydrochloride, dissolved in physiological saline (GlaxoSmithKline, Hertfordshire, UK) (n = 6) or saline (1 ml/kg) (n = 6). This particular dosage of Bup was chosen from literature (21, 34) and our laboratory's previous observation that this relatively low dose is sufficient to increase central neurotransmitter release (26).

Sampling.   During the experiments, microdialysis samples (20 µl) were collected every 20 min for 180 min. The samples were protected from oxidation by addition of 5 µl of antioxidant solution: L-cysteine (3.3 mM), Na2EDTA (0.27 mM), acetic acid (100 mM), ascorbic acid (0.0125 mM). Tbrain, Tcore, and Ttail, an index of heat loss response (10, 13), were measured every 20 min.

Chromatographic assays for the determination of NE, DA and 5-HT in dialysates from PO/AH.   For the analysis of NE, DA, and 5-HT, an offline microbore liquid chromatography assay was used with automatic injection (10 µl) of the samples, as described previously in detail (5, 31). In summary, the assay was based on ion-pair reverse-phase chromatography (C8, 5 µm; 100 x 1 mm), coupled to single-channel electrochemical detection (Decade, Leiden, The Netherlands). The mobile phase consisted of 27 ml acetonitrile and 200 ml of the following aqueous buffer: sodium acetate trihydrate (0.1 M), citric acid monohydrate (20 mM), decane sulfonic acid (2 mM), and sodium EDTA (0.5 mM) adjusted to pH 5.5. The flow rate through the column was 90 µl/min. Because of the high pH 5.5 of the mobile phase, a low oxidation potential was set (450 mV vs. Ag-AgCl). The retention times for NE, DA, and 5-HT were 3, 6, and 12 min, respectively with quantification limit for all compounds between 30 and 60 pM.

Histological examination.   At the end of each experiment, rats were killed with an overdose of pentobarbital sodium, and the brain was removed. The position of the microdialysis probe was verified in coronal sections (100 µm thick) stained with Chinese ink according to the coordinates described by Paxinos and Watson (23). We confirmed the location of the tip of microdialysis probe in the PO/AH. A photomicrograph of a sample section is shown in Fig. 1A, where the tip of location (arrow) and the width of the probe can be seen. Figure 1B is a diagrammatic representation of the tip locations in 12 experiments, where the tips are correctly positioned into the PO/AH.



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  		Fig. 1. A: typical photomicrograph showing the location of the microdialysis probe. Dye-stained dark area in the preoptic area and anterior hypothalamus (PO/AH) marks the position of the microdialysis probe (arrow). Coronal section (100 µm thick) is shown. f, Fornix; OC, optic chiasm. B: schematic representation of a sagittal section showing location of microdialysis probe tips. Each symbol ({blacksquare}, bupropion injections, n = 6; {circ}, saline injections, n = 6) indicates the location of the microdialysis probe successfully implanted into the PO/AH. AVPO, anteroventral preoptic area; AH, anterior hypothalamus; MPA, medial preoptic area; MPO, medial preoptic nucleus; LA, lateral anterior hypothalamus; SCh, suprachiasmatic nucleus; VMH, ventromedial hypothalamus.

 
Data collection and statistical analysis.   The average concentration of three microdialysis samples and temperature values for 1 h before drug administration was considered as the baseline and was defined as 100% or 0°C, respectively. Microdialysis samples and temperature values were expressed relative to this baseline value (means ± SE). Differences between data were evaluated for statistical significance by using two-factor (time and conditions) repeated-measures ANOVA followed by Bonferroni/Dunn post hoc tests. P < 0.05 was regarded as statistically significant.


   RESULTS
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 ABSTRACT
 MATERIALS AND METHODS
 RESULTS
DISCUSSION
 GRANTS
 ACKNOWLEDGMENTS
 REFERENCES
 
Figure 2 shows the mean changes in Tbrain (A), Tcore (B), and Ttail (C) before and after injection of Bup expressed at 20 min intervals. Injection of Bup influenced both Tbrain and Tcore, with values significantly elevated compared with the baseline value (Tbrain: 0.7 ± 0.1°C, Tcore: 0.5 ± 0.1°C, 40 min after injection; P < 0.05). These higher values of Tbrain and Tcore of Bup condition were significantly higher when compared with those recorded after saline treatment, and they were maintained until 100 and 120 min postinjection, respectively. Ttail was immediately decreased by the Bup injection, and a significant difference was found at 20 and 40 min (–1.9 ± 0.8°C, 40 min after injection; P < 0.05) compared with the baseline levels and the corresponding time of saline treatment. Saline injection did not change thermal parameters (n = 6).



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  		Fig. 2. Changes in brain temperature (A), core temperature (B), and tail skin temperature (C) by intraperitoneal injection of bupropion (17 mg/kg, {blacksquare}, n = 6) or saline (1 ml/kg, {circ}, n = 6). Values are means ± SE. Arrow indicates injection of bupropion or saline. *Significant differences from baseline values, P < 0.05. #Significant differences between the bupropion treatment and the corresponding time point in the saline group, P < 0.05.

 
Extracellular NE levels in the PO/AH increased significantly from 20 min after Bup injection compared with the baseline levels, reaching their highest value 40 min postinjection (466 ± 116%, Fig. 3A). These NE concentrations remained significantly elevated throughout the experiments (P < 0.05), and NE values were significantly higher at 20, 40, 60, and 80 min postinjection when compared with those recorded after saline treatment. Extracellular DA levels in the PO/AH increased significantly from 40 min after Bup injection (Fig. 3B). They remained significantly elevated until 100 min postinjection compared with the baseline levels (P < 0.05), and DA values were significantly higher at 40 and 60 min postinjection when compared with those recorded after saline treatment. The peak value of DA was observed 40 min postinjection (235 ± 45%, Fig. 3B). 5-HT showed no significant change after Bup injection (Fig. 3C). No such effect on neurotransmitters in the PO/AH was apparent under saline injection. Baseline levels of NE, DA, and 5-HT were 0.21 ± 0.1, 0.20 ± 0.1, and 0.25 ± 0.1 nM, respectively (n = 12).



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  		Fig. 3. Extracellular norepinephrine (NE; A), dopamine (DA; B), and serotonin (5-HT; C) in the PO/AH by intraperitoneal injection of bupropion (17 mg/kg, filled bars, n = 6) or saline (1 ml/kg, open bars, n = 6). Average concentration of 3 microdialysis samples before drug administration was considered as the baseline and was defined as 100%. Microdialysis samples were expressed relative to the baseline value (mean ± SE). Arrow indicates injection of bupropion or saline. *Significant differences from baseline values, P < 0.05. #Significant differences between the bupropion treatment and the corresponding time point in the saline group, P < 0.05. ^ Significant difference between NE and DA using unpaired t-test, P < 0.05.

 

   DISCUSSION
TOP
 ABSTRACT
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
GRANTS
 ACKNOWLEDGMENTS
 REFERENCES
 
The main finding of the present study was that an acute injection of Bup induced an increase in Tbrain and Tcore with a decrease in heat loss responses. These thermal responses were accompanied by an increase of the extracellular concentrations of NE and DA with no effect on 5-HT release in the PO/AH of freely moving rats measured via in vivo microdialysis.

Bup is a weak monoamine reuptake inhibitor that shows 2.5-fold selectivity for DA vs. NE and that has no effect on 5-HT (12, 30). Previous microdialysis studies have shown that acute doses of Bup have an effect on DA release in the rat striatum and nucleus accumbens in a dose-dependent manner (21) and on hippocampal NE and DA release of rats (26). It was also shown in mice that Bup (30 mg/kg ip) increased NE and DA release in the frontal cortex (40). In the present study, an acute injection of Bup increased the extracellular concentrations of NE and DA as well, but not of 5-HT, in the PO/AH (Fig. 3), which is comparable to the effect in the frontal cortex in mice (40). The NE increase was faster in onset (20 min) than the DA increase in the PO/AH, and NE releases were higher than those of DA. These results suggest that Bup influences more the noradrenergic neural activity than the dopaminergic neural activity in the hypothalamus.

The effects of Bup on thermoregulation have been previously reported in mice (39) and in rats (15, 16). Consistent with our observations, Liu et al. (15) demonstrated that oral administration of Bup increases colonic temperature in rats, with a rapid rise in oxygen consumption at a higher dose (30 mg/kg). These results imply that Bup has thermogenic properties in rats. However, there is no study that examined the effect of Bup on acute thermoregulatory responses and hypothalamic catecholamine levels in freely moving animals. In the present study, the acute injection of Bup increased NE and DA but not 5-HT in the PO/AH in rats, which caused heat production and thus increased Tbrain and Tcore. The decreased Ttail indicates a suppression of heat loss mechanisms, probably because of a vasoconstriction (8).

It is well known that NE, DA, and 5-HT in the hypothalamic regions play essential roles in several homeostatic functions, including thermoregulation (7, 36). For example, local application of NE into the rat PO/AH causes an increase in Tcore (4), and NE inhibits the activities of warm-sensitive neurons in the PO/AH (36). These findings suggest that NE is involved in heat production mechanisms. On the other hand, Quan et al. (28, 29) have shown that NE microdialyzed into the preoptic area of conscious guinea pigs evokes a fall in Tcore that is mediated by a reduction in metabolic rate. It has also been reported that DA excites the firing rate of warm-sensitive neurons but inhibits cold-sensitive neurons in tissue slices of the PO/AH (32). In addition, microinjections of DA or apomorphine, a DA agonist, into the hypothalamus and substantia nigra of the rat produced a DA-mediated decrease in temperature (3, 7). Moreover, DA release in the PO/AH is enhanced during treadmill exercise (9) and DA induces an increase in Tcore in rats (19). Thus the specific role that these monoamines play in the hypothalamus remains unclear. However, the present results suggest that both NE and DA or one of the two might be involved not only in thermogenesis but also in heat dissipation because Ttail immediately dropped after Bup injection.

Several studies have examined the relationship between 5-HT and thermoregulation as well. Local application of 5-HT into the PO/AH was reported to alter the activities of thermosensitive neurons (36). In the present study, although Tbrain, Tcore, and Ttail were influenced by acute injection of Bup, the extracellular 5-HT in the PO/AH remained unaltered. In addition, our laboratory's recent study showed that the perfusion of a 5-HT reuptake inhibitor or 5-HT1A agonist, into the PO/AH did not affect Tcore despite the fact that extracellular 5-HT in the PO/AH was increased or decreased (13). Therefore, hypothalamic 5-HT does not seem to mediate thermoregulation in response to immediate fluctuations in temperature, and 5-HT in the PO/AH is not involved in the Bup-induced increase in Tcore.

Different reuptake inhibitors in humans have been used to evaluate the effects of an increased neurotransmission on exercise performance and on CNS fatigue (17, 18, 22, 24, 25, 27, 33, 38). Recently, we found that acute ingestion of Bup improved time trial exercise performance of cyclists in a warm environment (30°C) (37). However, this increased performance was accompanied by a rise in rectal temperature during exercise reaching 40°C or above. Noteworthy, this response appeared to occur without any change in the subjective sensation. These results suggest that during exercise in the heat, Bup may override the inhibitory signals arising from the CNS that induce to stop exercising when close to the critical temperature. The pharmacological profile of Bup is different in animals and humans due to the fact that rodents lack hydroxybupropion, the major metabolite of Bup (6). However, if the results of the present study can be transposed to humans, they suggest that Bup probably also increases human brain temperature.

Conclusion.   The data from this study suggest that acute injection of Bup acts on the brain and affects brain and core temperatures through an increase in NE and DA release in the PO/AH. Further studies are necessary to elucidate the exact role of both neurotransmitter systems in heat production and heat loss mechanisms.


   GRANTS
TOP
 ABSTRACT
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 GRANTS
ACKNOWLEDGMENTS
 REFERENCES
 
This project was partially supported by research funding from the Vrije Universiteit Brussel (Grant OZR 990) and the Japanese Society for the Promotion of Science Postdoctoral Fellowships for Research Abroad.


   ACKNOWLEDGMENTS
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 ABSTRACT
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 GRANTS
 ACKNOWLEDGMENTS
REFERENCES
 
The authors appreciate the excellent technical assistance provided by G. De Smet, R. Clinckers, R. M. Geens, R. Berckmans, and C. De Rijck.


   FOOTNOTES
 

Address for reprint requests and other correspondence: R. Meeusen, Dept. of Human Physiology and Sportsmedicine, Vrije Universiteit Brussel, Pleinlaan 2, 1050 Brussels, Belgium (e-mail: rmeeusen{at}vub.ac.be)

The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.


   REFERENCES
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 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 GRANTS
 ACKNOWLEDGMENTS
 REFERENCES
 

  1. Ascher JA, Cole JO, Colin JN, Feighner JP, Ferris RM, Fibiger HC, Golden RN, Martin P, Potter WZ, and Richelson E. Bupropion: a review of its mechanisms and antidepressant activity. J Clin Psychiatry 56: 395–401, 1995.[Web of Science][Medline]
  2. Boulant JA and Dean JB. Temperature receptors in the central nervous system. Annu Rev Physiol 46: 639–654, 1986.[CrossRef]
  3. Brown SJ, Gisolfi CV, and Mora F. Temperature regulation and dopaminergic systems in the brain: does the substantia nigra play a role? Brain Res 234: 275–286, 1982.[CrossRef][Web of Science][Medline]
  4. Clark WG and Lipton JM. Changes in body temperature after administration of adrenergic and serotonergic agents and related drugs including antidepressants: II. Neurosci Biobehav Rev 10: 153–220, 1986.[CrossRef][Web of Science][Medline]
  5. Clinckers R, Smolders I, Meurs A, Ebinger G, and Michotte Y. Anticonvulsant action of hippocampal dopamine and serotonin is independently mediated by DA and 5-HT receptors. J Neurochem 89: 834–843, 2004.[CrossRef][Medline]
  6. Cooper BR, Wang CM, Cox RF, Norton R, Shea V, and Ferris RM. Evidence that the acute behavioral and electrophysiological effects of bupropion (Wellbutrin) are mediated by a noradrenergic mechanism. Neuropharmacology 11: 133–141, 1994.
  7. Cox B and Lee TF. Further evidence for a physiological role for hypothalamic dopamine in thermoregulation in the rat. J Physiol 300: 7–17, 1980.[Abstract/Free Full Text]
  8. Gordon CJ. Thermal biology of the laboratory rat. Physiol Behav 47: 963–991, 1990.[CrossRef][Medline]
  9. Hasegawa H, Yazawa T, Yasumatsu M, Otokawa M, and Aihara Y. Alteration in dopamine metabolism in the thermoregulatory center of exercising rats. Neurosci Lett 289: 161–164, 2000.[CrossRef][Web of Science][Medline]
  10. Hasegawa H, Ishiwata T, Saito T, Yazawa T, Aihara Y, and Meeusen R. Inhibition of the preoptic area and anterior hypothalamus by tetrodotoxin alters thermoregulatory functions in exercising rats. J Appl Physiol 98: 1458–1462, 2005.[Abstract/Free Full Text]
  11. Hillegaart V. Effects of local application of 5-HT and 8-OH-DPAT into the dorsal and median raphe nuclei on core temperature in the rat. Psychopharmacology (Berl) 103: 291–296, 1991.[CrossRef][Medline]
  12. Hyttel J. Citalopram—pharmacological profile of a specific serotonin uptake inhibitor with antidepressant activity. Prog Neuropsychopharmacol Biol Psychiatry 6: 277–295, 1982.[CrossRef][Medline]
  13. Ishiwata T, Saito T, Hasegawa H, Yazawa T, Otokawa M, and Aihara Y. Changes of body temperature and extracellular serotonin level in the preoptic area and anterior hypothalamus after thermal or serotonergic pharmacological stimulation of freely moving rats. Life Sci 75: 2665–2675, 2004.[CrossRef][Web of Science][Medline]
  14. Jacobs BL and Azmitia EC. Structure and function of the brain serotonin system. Physiol Rev 72: 165–229, 1992.[Free Full Text]
  15. Liu YL, Connoley IP, Harrison J, Heal DJ, and Stock MJ. Comparison of the thermogenic and hypophagic effects of sibutramine's metabolite 2 and other monoamine reuptake inhibitors. Eur J Pharmacol 452: 49–56, 2002.[CrossRef][Medline]
  16. Liu YL, Connoley IP, Harrison J, Heal DJ, and Stock MJ. Pharmacological characterization of the thermogenic effect of bupropion. Eur J Pharmacol 498: 219–225, 2004.[Medline]
  17. Meeusen R, Roeykens J, Magnus L, Keizer H, and De Meirleir K. Endurance performance in humans: the effect of a dopamine precursor or a specific serotonin (5-HT2A/2C) antagonist. Int J Sports Med 18: 571–577, 1997.[Web of Science][Medline]
  18. Meeusen R, Piacentini MF, Van Den Eynde S, Magnus L, and De Meirleir K. Exercise performance is not influenced by a 5-HT reuptake inhibitor. Int J Sports Med 22: 329–336, 2001.[CrossRef][Web of Science][Medline]
  19. Myers RD and Yaksh TL. Feeding and temperature responses in the unrestrained rat after injections of cholinergic and aminergic substances into the cerebral ventricles. Physiol Behav 3: 917–928, 1968.[CrossRef]
  20. Nestler EJ, Hyman SE, and Malenka RC. Molecular Neuropharmacology: A Foundation for Clinical Neuroscience. New York: McGraw-Hill, 2001.
  21. Nomikos GG, Damsma G, Wenkstern D, and Fibiger HC. Acute effects of bupropion on extracellular dopamine concentrations in rat striatum and nucleus accumbens studied by in vivo microdialysis. Neuropsychopharmacology 2: 273–279, 1989.[CrossRef][Web of Science][Medline]
  22. Pannier JL, Bouckaert JJ, and Lefebvre RA. The antiserotonin agent pizotifen does not increase endurance performance in humans. Eur J Appl Physiol 72, 175–178, 1995.[CrossRef]
  23. Paxinos G and Watson C. The Rat Brain in Stereotaxic Coordinates (2nd ed.). Sydney, Australia: Academic, 1986.
  24. Piacentini MF, Meeusen R, Buyse L, De Schutter G, Kempenaers F, Van Nijvel J, and De Meirleir K. No effect of a noradrenergic reuptake inhibitor on performance in trained cyclists. Med Sci Sports Exerc 34: 1189–1193, 2002a.
  25. Piacentini MF, Meeusen R, Buyse L, De Schutter G, and De Meirleir K. No effect of a selective serotonergic/noradrenergic reuptake inhibitor on endurance performance. Eur J Sports Sci 2: 1–10, 2002.
  26. Piacentini MF, Clinckers R, Meeusen R, Sarre S, Ebinger G, and Michotte Y. Effect of bupropion on hippocampal neurotransmitters and on peripheral hormonal concentrations in the rat. J Appl Physiol 95: 652–656, 2003.[Abstract/Free Full Text]
  27. Piacentini MF, Meeusen R, Buyse L, De Schutter G, and De Meirleir K. Hormonal responses during prolonged exercise are influenced by a selective dopamine/noradrenaline reuptake inhibitor. Br J Sports Med 38: 129–133, 2004.[Abstract/Free Full Text]
  28. Quan N, Xin L, and Blatteis CM. Microdialysis of noradrenaline into preoptic area of guinea pigs: characteristics of hypothermic effect. Am J Physiol Regul Integr Comp Physiol 261: R378–R385, 1991.[Abstract/Free Full Text]
  29. Quan N, Xin L, Ungar AL, and Blatteis CM. Preoptic noradrenaline-induced hypothermia is mediated by {alpha}2-adrenoceptors. Am J Physiol Regul Integr Comp Physiol 262: R407–R411, 1992.[Abstract/Free Full Text]
  30. Richelson E and Pfenning M. Blockade by antidepressants and related compounds of biogenic amine uptake into rat brain synaptosomes: most antidepressants selectively block noradrenaline uptake. Eur J Pharmacol 104: 277–286, 1984.[CrossRef][Web of Science][Medline]
  31. Sarre S, Thorre K, Smolders I, and Michotte Y. Microbore liquid chromatography analysis of monoamine transmitters. Methods Mol Biol 72: 185–196, 1997.[Medline]
  32. Scott IM and Boulant JA. Dopamine effects on thermosensitive neurons in hypothalamic tissue slices. Brain Res 306: 157–163, 1984.[CrossRef][Medline]
  33. Struder HK, Hollman W, Platen P, Duperly J, Fischer HG, and Weber K. Influence of paroxetine, branched-chain amino acids and tyrosine on neuroendocrine system responses and fatigue in humans. Horm Metab Res 30: 188–194, 1998.[Web of Science][Medline]
  34. Terry P and Katz JL. Dopaminergic mediation of the discriminative stimulus effects of bupropion in rats. Psychopharmacology (Berl) 134: 201–212, 1997.[CrossRef][Medline]
  35. Van Hemelrijck AV, Vermijlen D, Hachimi-Idrissi S, Sarre S, Ebinger G, and Michotte Y. Effects of resuscitative mild hypothermia on glutamate and dopamine release, apoptosis and ischaemic brain damage in the endothelin-1 rat model for focal cerebral ischaemia. J Neurochem 87: 66–75, 2003.[CrossRef][Medline]
  36. Watanabe T, Morimoto A, and Murakami N. Effect of amine on temperature-responsive neuron in slice preparation of rat brain stem. Am J Physiol Regul Integr Comp Physiol 250: R553–R559, 1986.[Abstract/Free Full Text]
  37. Watson P, Hasegawa H, Roelands B, Piacentini MF, Looverie R, and Meeusen R. Acute dopamine / noradrenaline reuptake inhibition enhances exercise performance in warm, but not temperate conditions. J Physiol 565: 873–883, 2005.[Abstract/Free Full Text]
  38. Wilson W and Maughan R. Evidence for a possible role of 5-hydroxytryptamine in the genesis of fatigue in man: administration of paroxetine, a 5-HT re-uptake inhibitor, reduces the capacity to perform prolonged exercise. Exp Physiol 77: 921–924, 1992.[Abstract]
  39. Zarrindast MR and Abolfathi-Araghi F. Effects of bupropion on core body temperature of mice. Psychopharmacol 106: 248–252, 1992.[Medline]
  40. Zocchi A, Varnier G, Arban R, Griffante C, Zanetti L, Bettelini L, Marchi M, Gerrard PA, and Corsi M. Effects of antidepressant drugs and GR 205171, an neurokinin-1 (NK1) receptor antagonist, on the response in the forced swim test and on monoamine extracellular levels in the frontal cortex of the mouse. Neurosci Lett 345: 73–76, 2003.[CrossRef][Medline]



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H. Hasegawa, M. F. Piacentini, S. Sarre, Y. Michotte, T. Ishiwata, and R. Meeusen
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