Effect of Activation of the GLT-1 Transporter by a Beta-Lactam Antibiotic on Serotonin-Induced Scratching Behavior in Mice
Glutamate is believed to be the predominant excitatory neurotransmitter in the networks responsible for itch-related behavior. Beta-lactam antibiotics were shown to exert neuroprotective effects by increasing expression of the glutamate transporter GLT-1. We observed whether repeated administrati...
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irk-123456789-1481572019-02-18T01:24:03Z Effect of Activation of the GLT-1 Transporter by a Beta-Lactam Antibiotic on Serotonin-Induced Scratching Behavior in Mice Gunduz, O. Topuz, R.D. Todurga, Z.G. Duvan, K. Karadag, C.H. Ulugol, A. Glutamate is believed to be the predominant excitatory neurotransmitter in the networks responsible for itch-related behavior. Beta-lactam antibiotics were shown to exert neuroprotective effects by increasing expression of the glutamate transporter GLT-1. We observed whether repeated administration of the beta-lactam antibiotic ceftriaxone suppresses serotonin-induced itch-related behavior (similarly to its effect on pain transmission) in mice. Chronic, but not acute, ceftriaxone introductions reduced the number of serotonin-induced scratches; dihydrokainic acid, a selective GLT-1 transporter inhibitor, partly but significantly abolished this effect of ceftriaxone. Our findings suggest that GLT-1 activation by beta-lactam antibiotics looks promising for the treatment of chronic itch. Як вважають, глутамат є основним збуджуючим нейротрансмітером у нейронних мережах, відповідальних за поведінкові моторні прояви при почутті свербіжу. β-лактамні антибіотики мають нейропротективні властивості, оскільки забезпечують посилену експресію глутаматного транспортера GLT-1. Ми з’ясовували, чи здатне повторне введення β-лактамного антибіотика цефтриаксону пригнічувати викликані ін’єкціями серотоніну поведінкові моторні прояви (чухальні рухи), пов’язані з індукцією почуття свербіжу (подібно до впливу цього агента на біль) у мишей. Хронічні (але не поодинокі) введення цефтриаксону викликали зменшення кількості рухів чухання. Селективний блокатор транспортера GLT-1 дигідрокаїнова кислота частково, але істотно перешкоджала цьому ефекту цефтриаксону. Наші спостереження дають підстави вважати, що активація GLT-1 β-лактамними антибіотиками є перспективним підходом у лікуванні хронічного свербіжу. 2015 Article Effect of Activation of the GLT-1 Transporter by a Beta-Lactam Antibiotic on Serotonin-Induced Scratching Behavior in Mice / O. Gunduz, R.D. Topuz, Z.G. Todurga, K. Duvan, C.H. Karadag, A. Ulugol // Нейрофизиология. — 2015. — Т. 47, № 1. — С. 45-48. — Бібліогр.: 21 назв. — англ. 0028-2561 http://dspace.nbuv.gov.ua/handle/123456789/148157 577.175.823:829 en Нейрофизиология Інститут фізіології ім. О.О. Богомольця НАН України |
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Digital Library of Periodicals of National Academy of Sciences of Ukraine |
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English |
| description |
Glutamate is believed to be the predominant excitatory neurotransmitter in the networks
responsible for itch-related behavior. Beta-lactam antibiotics were shown to exert
neuroprotective effects by increasing expression of the glutamate transporter GLT-1. We
observed whether repeated administration of the beta-lactam antibiotic ceftriaxone suppresses
serotonin-induced itch-related behavior (similarly to its effect on pain transmission) in mice.
Chronic, but not acute, ceftriaxone introductions reduced the number of serotonin-induced
scratches; dihydrokainic acid, a selective GLT-1 transporter inhibitor, partly but significantly
abolished this effect of ceftriaxone. Our findings suggest that GLT-1 activation by beta-lactam
antibiotics looks promising for the treatment of chronic itch. |
| format |
Article |
| author |
Gunduz, O. Topuz, R.D. Todurga, Z.G. Duvan, K. Karadag, C.H. Ulugol, A. |
| spellingShingle |
Gunduz, O. Topuz, R.D. Todurga, Z.G. Duvan, K. Karadag, C.H. Ulugol, A. Effect of Activation of the GLT-1 Transporter by a Beta-Lactam Antibiotic on Serotonin-Induced Scratching Behavior in Mice Нейрофизиология |
| author_facet |
Gunduz, O. Topuz, R.D. Todurga, Z.G. Duvan, K. Karadag, C.H. Ulugol, A. |
| author_sort |
Gunduz, O. |
| title |
Effect of Activation of the GLT-1 Transporter by a Beta-Lactam Antibiotic on Serotonin-Induced Scratching Behavior in Mice |
| title_short |
Effect of Activation of the GLT-1 Transporter by a Beta-Lactam Antibiotic on Serotonin-Induced Scratching Behavior in Mice |
| title_full |
Effect of Activation of the GLT-1 Transporter by a Beta-Lactam Antibiotic on Serotonin-Induced Scratching Behavior in Mice |
| title_fullStr |
Effect of Activation of the GLT-1 Transporter by a Beta-Lactam Antibiotic on Serotonin-Induced Scratching Behavior in Mice |
| title_full_unstemmed |
Effect of Activation of the GLT-1 Transporter by a Beta-Lactam Antibiotic on Serotonin-Induced Scratching Behavior in Mice |
| title_sort |
effect of activation of the glt-1 transporter by a beta-lactam antibiotic on serotonin-induced scratching behavior in mice |
| publisher |
Інститут фізіології ім. О.О. Богомольця НАН України |
| publishDate |
2015 |
| url |
http://dspace.nbuv.gov.ua/handle/123456789/148157 |
| citation_txt |
Effect of Activation of the GLT-1 Transporter by a Beta-Lactam Antibiotic on Serotonin-Induced Scratching Behavior in Mice / O. Gunduz, R.D. Topuz, Z.G. Todurga, K. Duvan, C.H. Karadag, A. Ulugol // Нейрофизиология. — 2015. — Т. 47, № 1. — С. 45-48. — Бібліогр.: 21 назв. — англ. |
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Нейрофизиология |
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NEUROPHYSIOLOGY / НЕЙРОФИЗИОЛОГИЯ.—2015.—T. 47, № 1 45
UDC 577.175.823:829
O. GUNDUZ1, R. D. TOPUZ1, Z. G. TODURGA1, K. DUVAN1, C. H. KARADAG1, A. ULUGOL1
EFFECT OF ACTIVATION OF THE GLT-1 TRANSPORTER BY A BETA-LACTAM
ANTIBIOTIC ON SEROTONIN-INDUCED SCRATCHING BEHAVIOR IN MICE
Received February 17, 2014
Glutamate is believed to be the predominant excitatory neurotransmitter in the networks
responsible for itch-related behavior. Beta-lactam antibiotics were shown to exert
neuroprotective effects by increasing expression of the glutamate transporter GLT-1. We
observed whether repeated administration of the beta-lactam antibiotic ceftriaxone suppresses
serotonin-induced itch-related behavior (similarly to its effect on pain transmission) in mice.
Chronic, but not acute, ceftriaxone introductions reduced the number of serotonin-induced
scratches; dihydrokainic acid, a selective GLT-1 transporter inhibitor, partly but significantly
abolished this effect of ceftriaxone. Our findings suggest that GLT-1 activation by beta-lactam
antibiotics looks promising for the treatment of chronic itch.
Keywords: ceftriaxone, glutamate transporter GLT-1, itch, serotonin.
1Department of Medical Pharmacology, Faculty of Medicine, Trakya
University, Edirne (Turkey).
Correspondence should be addressed to (A. Ulugol)
(e-mail: aulugol@trakya.edu.tr ; aulugol@yahoo.com).
INTRODUCTION
Glutamate is known to be a principal excitatory amino
acid neurotransmitter in the CNS. A few glutamate
transporters found in neuronal and glial membranes
are primarily responsible for the regulation of
extracellular glutamate homeostasis. Among these
transporters, glutamate transporter-1 (GLT-1) removes
at least 90% of extracellular glutamate and appears to
play the pivotal role in terminating synaptic effects
of this acid transmitter [1, 2]. Accordingly, drugs
stimulating the GLT-1 expression are shown to offer
neuroprotection [3]. Among these agents, ceftriaxone,
a popular beta-lactam antibiotic, is being widely
studied. It is suggested to contribute to possible effects
in many clinical CNS disorders, including Parkinson’s
disease, stroke, epilepsy, visceral and neuropathic
pain, and tolerance and dependence to drugs affecting
the CNS [3-9]. In addition, it is under clinical trials
for the treatment of amyotrophic lateral sclerosis.
Itch is an unpleasant (but protective) sensation that
provokes the desire to scratch. Although pain and itch
are distinct sensations, most noxious chemicals appear
to be nonspecific with respect to these phenomena;
moreover, spinal cord neuronal mechanisms are
suggested to play a pivotal role not only in pain, but
also in itch [10, 11]. Recent researches showed that,
similarly to pain sensation, glutamate acts as the major
excitatory transmitter for synaptic transmission in the
networks involved in the itch-related behavior [12]. As
a result, the directions of antipruritic therapies are now
expanding from the periphery (skin) to the CNS [13,
14]. Taking into consideration the similarities between
itch and pain sensations, we investigated the effect of
activation of the GLT-1 transporter by ceftriaxone on
serotonin-induced scratching behavior in mice.
METHODS
Eight- to 12-week-old male Balb/c mice (Center of
the Laboratory Animals, Trakya University) were
used in the experiments. Animals were maintained
under a controlled light cycle (12-12 h light-dark) and
temperature (21 ± 2°C) with water and food available
ad libitum.
To provoke scratching behavior, 50 µg/50 µl of
serotonin was injected intradermally into the rostral
part of the back of the experimental mice. Immediately
after serotonin administration, the animals were put
back into the same cages, and their behavior was
videotaped for 30 min; the experimenters remained
outside the laboratory during this period. The number
of scratching of the injected site by the hindpaws
within the observation period was counted as an index
of the scratching intensity.
NEUROPHYSIOLOGY / НЕЙРОФИЗИОЛОГИЯ.—2015.—T. 47, № 146
O. GUNDUZ, R. D. TOPUZ, Z. G. TODURGA at al.
Naive mice were i.p. injected with either saline or
ceftriaxone (50, 100, or 200 mg/kg) once daily for
7 days. On day 7, scratching behavior was induced
by serotonin administration 30 min after ceftriaxone
injection. In a separate animal group, a single injection
of ceftriaxone (200 mg/kg, i.p.) was administered in
order to evaluate its acute effect. To determine if GLT-1
activation mediates the ceftriaxone effect, the GLT-1
blocker, dihydrokainic acid (DHKA, 10 mg/kg, i.p.),
was co-administered with ceftriaxone for 7 days. Drug
doses and treatment times were chosen according to
previous reports [5, 6, 15].
A commercial preparation of ceftriaxone (Rocephin,
Roche, France) was used; DHKA was purchased from
Tocris (Great Britain). Ceftriaxone and DHKA were
dissolved in saline and administered i.p. in a volume
of 0.1 ml/10 g body mass.
Analysis of variance (ANOVA) was used to carry
out statistical comparisons among groups and followed
by the Bonferroni t-test. Differences with P values
< 0.05 were considered to be statistically significant.
All data are expressed below as means ± s.e.m.
RESULTS
In the control group of serotonin-injected mice, the
mean number of scratches within the 30-min-long
observation period was 46.6 ± 7.6 (Fig. 1, 1). In the
groups treated with 50 and 100 mg/kg ceftriaxone,
the number of scratches was by about 60% smaller
than in the control (P < 0.05; Fig. 1, 2 and 3). In the
group treated with the greatest dose of ceftriaxone
(200 mg/kg), the intensity of suppression of scratching
was higher, more than fourfold (P < 0.01; Fig. 1, 4).
Single injections of 200 mg/kg ceftriaxone provided
some trend toward decrease in the number of scratches,
but the difference from the control was insignificant
(Fig. 1, 5). Isolated injections of DHKA decreased
somewhat the number of scratches. The decrement
was about 22%, but the difference was insignificant
(mostly because of considerable interindividual
dispersion of the values; Fig. 1, 6). Introductions
of DHKA combined with chronic injections of high
doses of ceftriaxone (200 mg/kg) partly but rather
significantly suppressed the protective effect of the
above antibiotic. In the respective group, the number
of scratches within the observation interval was about
60% of the control, i.e., the intensity of scratching was
2.5 times higher than in the group chronically treated
with 200 mg/kg ceftriaxone but with no action of the
above GLT-1 transporter inhibitor.
Therefore, ceftriaxone introductions reduced
serotonin-induced scratching behavior with all the
doses used, but only under condition of repeated
(chronic) injections. Certain dose dependence was
observed in this case; the highest doses (200 mg/kg)
provided the greatest anti-itch effect; at the same time,
the dependence at smaller doses was not obvious. The
GLT-1 transporter inhibitor DHKA (10 mg/kg) elicited
nearly no action in the case of isolated introduction
but significantly abolished the inhibitory effect of
ceftriaxone. No significant protective effect was
observed in the case of acute ceftriaxone treatment.
DISCUSSION
Pain and itch are distinct but, at the same time, partly
similar sensations, both switching on the alert systems
to protect the organism of vertebrates from some
noxious stimuli. In the periphery, noxious chemicals
are not very specific with respect to pain or itch, and
TRP channels are shown to be involved in mediating
of both these phenomena [10, 16]. Distinct subsets of
itch-specific C-fibers transmit signals from the skin
to the superficial spinal dorsal horn regions [17, 18]
and, subsequently, to the thalamus and some other
suprasegmental structures [11, 18].
Spinal dorsal horn neuronal networks attract great
1
*
*
**
+
2 3 4 5 6 7
20
0
40
60
Diagram of the number of scratches performed by serotonin-ijected
mice within the 30-min-long observation period. 1-7) Experimental
groups, control (1), repeatedly injected with 50, 100, and 200 mg/kg
ceftriaxone daily during 7 days (2-4, respectively), subjected to
single 200 mg/kg ceftriaxon injections (5), to isolated 10 mg/kg
DHKA injections (6), and to combined repeated injections of 200
mg/kg ceftriaxone and 10 mg/kg DHKA (7).
Діаграма кількості чухальних рухів у мишей після ін’єкції
серотоніну протягом 30-хвилинного періоду спостереження.
NEUROPHYSIOLOGY / НЕЙРОФИЗИОЛОГИЯ.—2015.—T. 47, № 1 47
EFFECT OF ACTIVATION OF THE GLT-1 TRANSPORTER BY A BETA-LACTAM ANTIBIOTIC
attention of researchers, since these networks are sug-
gested to play important roles in the formation of both
pain and itch sensations [10, 11, 13]. Spinal opioids,
gastrin-releasing peptide (GRP), glutamate, bradyki-
nin, substance P, serotonin, and histamine receptors
were shown (or expected) to be involved in itch, and
targeting these spinal receptors by pharmacological
agents seems promising for the development of new
antipruritic drugs [14]. In addition, first inhibitory in-
terneurons in itch-related networks have been iden-
tified in the dorsal spinal cord; loss or suppression of
inhibition has been shown to cause pathological itch,
similarly to abnormal pain [19]. Deletion of vesicu-
lar GLT-2 in the dorsal root ganglia augmented beha-
vioral itch responses [20, 21]. Accordingly, similarly
to the pain sensation, glutamate is proposed to be the
major neurotransmitter for both GRP-sensitive and in-
sensitive itch-related synaptic transmission in the spi-
nal cord [12].
Chronic introductions of ceftriaxone were shown
to exert anti-nociceptive effects in neuropathic rats;
the respective events were considered resulting from
specific up-regulation of GLT-1 expression in the spi-
nal cord [8]. When the importance of the amount of
released glutamate in the spinal dorsal horn for the
itch phenomena is taken into consideration, it can be
speculated that isolated action of DHKA should induce
scratching behavior. However, we did not observe such
effect after isolated administration of this agent. This
may be related to an insufficient dose of DHKA. It
should also be mentioned that the same dose of the
above drug was used in pain studies without any effect
on nociception [4-6].
Thus, we found that serotonin-induced scratching
behavior is suppressed due to repeated treatment with
ceftriaxone. In addition to increased expression and
function of the GLT-1 in the brain, chronic ceftriaxone
administration may also provide GLT-1 up-regulation
in the spinal dorsal horn. Although the mechanism of
anti-pruritic activity of the tested beta-lactam antibiotic
awaits further exploration, our results indicate that
GLT-1 activation by this agent may be a promising op-
tion in pharmacotherapy of some chronic itch states.
The study was carried out in accordance with the statements
of the Council Directive regarding the protection of animals
used for experimental and other scientific purposes (86/609/
EEC, 1986, Strasbourg). It was approved by the Animal Care
Ethics Committee at the Trakya University, and conducted
according to the guidelines of the Ethical Committee of the
International Association for the study of pain.
The authors of this study, O. Gunduz, R. D. Topuz,
Z. G. Todurga, K. Duvan, C. H. Karadag, and A. Ulugol,
confirm that the research and publication of the results were not
associated with any conflicts regarding commercial or financial
relations, relations with organizations and/or individuals who
may have been related to the study, and interrelations of co-
authors of the article.
О. Гундуз1, Р. Д. Тонуз1, З. Г. Тодурга1, К. Дуван1, С. Х. Ка-
радаг1, А. Улугал1
ВПЛИВ АКТИВАЦІЇ ГЛУТАМАТНОГО ТРАНСПОР-
ТЕРА-1 β-ЛАКТАМНИМ АНТИБІОТИКОМ НА
ВИКЛИКАНІ СЕРОТОНІНОМ ЧУХАЛЬНІ РУХИ
У МИШЕЙ
1 Фракійський Університет, Едірне (Туреччина).
Р е з ю м е
Як вважають, глутамат є основним збуджуючим нейротранс-
мітером у нейронних мережах, відповідальних за поведін-
кові моторні прояви при почутті свербіжу. β-лактамні ан-
тибіотики мають нейропротективні властивості, оскільки
забезпечують посилену експресію глутаматного транспор-
тера GLT-1. Ми з’ясовували, чи здатне повторне введення
β-лактамного антибіотика цефтриаксону пригнічувати ви-
кликані ін’єкціями серотоніну поведінкові моторні про-
яви (чухальні рухи), пов’язані з індукцією почуття свербі-
жу (подібно до впливу цього агента на біль) у мишей. Хро-
нічні (але не поодинокі) введення цефтриаксону викликали
зменшення кількості рухів чухання. Селективний блокатор
транспортера GLT-1 дигідрокаїнова кислота частково, але
істотно перешкоджала цьому ефекту цефтриаксону. Наші
спостереження дають підстави вважати, що активація GLT-1
β-лактамними антибіотиками є перспективним підходом у
лікуванні хронічного свербіжу.
REFERENCES
1. N. C. Danbolt, “Glutamate uptake,” Prog. Neurobiol., 65,
No. 1, 1-105 (2001).
2. R. P. Seal and S. G. Amara, “Excitatory amino acid
transporters: A family in flux,” Annu. Rev. Pharmacol., 39,
431-456 (1999).
3. J. D. Rothstein, S. Patel, and M. R. Regan, et al., “Beta-lactam
antibiotics offer neuroprotection by increasing glutamate
transporter expression,” Nature, 433, No. 7021, 73-77 (2005).
4. S. M. Rawls, M. Zielinski, H. Patel, et al., “Beta-lactam
antibiotic reduces morphine analgesic tolerance in rats
through GLT-1 transporter activation,” Drug Alcohol
Dependence, 107, Nos. 2/3, 261-263 (2010).
5. O. Gunduz, C. Oltulu, D. Buldum, et al., “Anti-allodynic and
anti-hyperalgesic effects of ceftriaxone in streptozocin-induced
diabetic rats,” Neurosci. Lett., 491, No. 1, 23-25 (2011).
6. O. Gunduz, C. Oltulu, and A. Ulugol, “Role of GLT-
NEUROPHYSIOLOGY / НЕЙРОФИЗИОЛОГИЯ.—2015.—T. 47, № 148
O. GUNDUZ, R. D. TOPUZ, Z. G. TODURGA at al.
1 transporter activation in prevention of cannabinoid
tolerance by the beta-lactam antibiotic, ceftriaxone, in mice,”
Pharmacol. Biochem. Behav., 99, No. 1, 100-103 (2011).
7. A. Ulugol, “Reduction of dependence to cannabinoids by
GLT-1 activating property of the beta-lactam antibiotic,” Med.
Hypoth., 80, No. 3, 247-248 (2013).
8. Y. Hu, W. Li, L. Lu, et al., “An anti-nociceptive role for
ceftriaxone in chronic neuropathic pain in rats,” Pain, 148,
No. 2, 284-301 (2010).
9. V. L. Rao, K. K. Bowen, and R. J. Dempsey, “Transient
focal cerebral ischemia down-regulates glutamate trans-
porters GLT-1 and EAAC1 expression in rat brain,”
Neurochem. Res., 26, No. 5, 497-502 (2001).
10. S. E. Ross, “Pain and itch: insights into the neural
circuits of aversive somatosensation in health and disease,”
Current Opin. Neurobiol., 2, No. 6, 880-887 (2011).
11. M. Schmelz, “Itch and pain,” Neurosci. Biobehav. Rev., 34,
No. 2, 171-176 (2010).
12. K. Koga, T. Chen, X.-Y. Li, et al., “Glutamate acts as a
neurotransmitter for gastrin releasing peptide-sensitive
and insensitive itch-related synaptic transmission in
mammalian spinal cord,” Mol. Pain, 7, 47 (2011).
13. T. Andoh, Y. Gotoh, and Y. Kuraishi, “Milnacipran ınhibits
ıtch-related responses in mice through the enhancement
of noradrenergic transmission in the spinal cord,” J.
Pharmacol. Sci., 123, No. 2, 199-202 (2013).
14. F. Cevikbas, M, Steinhoff, and A. Ikoma, “Role of spinal
neurotransmitter receptors in itch: New ınsights into therapies
and drug development,” CNS Neurosci. Ther., 17, No. 6, 742-
749 (2011).
15. I. Karaman, G. Kizilay-Ozfidan, C. H. Karadag, and A. Ulugol,
“Lack of effect of ceftriaxone, a GLT-1 transporter activator,
on spatial memory in mice,” Pharmacol. Biochem. Behav.,
108, 61-65 (2013).
16. B. L. Xiao and A. Patapoutian, “Scratching the surface: a role
of pain-sensing TRPA1 in itch,” Nat. Neurosci., 14, No. 5,
540-542 (2011).
17. D. Andrew and A. D. Craig, “Spinothalamic lamina I
neurons selectively sensitive to histamine: a central neu-
ral pathway for itch,” Nat. Neurosci., 4, No. 1, 72-77 (2001).
18. A. Ikoma, M. Steinhoff, S. Stander, et al., “The neurobiology
of itch,” Nat. Rev. Neurosci., 7, No. 7, 535-547 (2006).
19. S. E. Ross, A. R. Mardinly, A. E. McCord, et al., “Loss
of inhibitory interneurons in the dorsal spinal cord and
elevated itch in Bhlhb5 mutant mice,” Neuron, 65, No. 6,
886-898 (2010).
20. M. C. Lagerstrom, K. Rogoz, B. Abrahamsen, et al., “VGLUT2-
dependent sensory neurons in the TRPV1 population
regulate pain and ıtch,” Neuron, 68, No. 3, 529-542 (2010).
21. Y. Liu, O. Abdel Samad, L. Zhang, et al., “VGLUT2-dependent
glutamate release from nociceptors is required to sense
pain and suppress itch,” Neuron, 68, No. 3, 543-556 (2010).
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