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Year 2014, Volume: 31 Issue: 1, 43 - 50, 05.06.2014

Abstract

References

  • Alajaji, M., Bowers, M.S., Knackstedt, L., Damaj, M.I., 2013. Effects of the beta-lactam antibiotic ceftriaxone on nicotine withdrawal and nico- tine-induced reinstatement of preference in mice. Psychol. 228, 419-426. doi:10.1007/s00213-013-3047-3043.
  • Bailey, K.R., Crawley, J.N., 2009. Anxiety-Related Behaviours in Mice. In: Buccafusco, J.J., editor. Methods of behaviour analysis in neuros- cience. 2nd edition. Boca Raton (FL): CRC Press; Chapter 5, 3-27.
  • Baumann, M.H., Clark, R.D., Rothman, R.B., 2008. Locomotor stimulation produced by 3,4-methylenedioxymethamphetamine (MDMA) is cor- related with dialysate levels of serotonin and dopamine in rat brain. Pharmacol. Biochem. Behav. 90, 208-217. doi:10.1016/ j.pbb.2008.02.018.
  • Bernabucci, M., Notartomaso, S., Zappulla, C., Fazio, F., Cannella, M., Motolese, M., Battaglia, G., Bruno, V., Gradini, R., Nicoletti, F., 2012. N-Acetyl-cysteine causes analgesia by reinforcing the endogenous activation of type-2 metabotropic glutamate receptors. Mol. Pain. 23, 77. doi: 10.1186/1744-8069-8-77.
  • Bridges, R., Lutgen, V., Lobner, D., Baker, D.A., 2012. Thinking outside the cleft to understand synaptic activity: Contribution of the cys- tine-glutamate antiporter (System xc-) to normal and pathological glutamatergic signaling. Pharmacol. Rev. 64, 780-802. doi:10.1124 / pr.110.003889.
  • However, chronic use of CTX, a parenteral antibiotic, is not
  • practical for routine treatment of behavioural disorders and
  • also may change the microflora of the gut in favour of a
  • superinfection and in addition to this, concern of antibiotic
  • resistance with the repeated doses of the drug should be kept
  • in mind. Given the role of EAATs to compartmentalize
  • glutamate into functionally distinct pools (e.g., synaptic,
  • extrasynaptic), it is possible that receptors located in the
  • synapse or in the extrasynaptic compartment are being
  • stimulated by glutamate diffusing across microdomains
  • (Bridges et al., 2012). It may be a further investigation area
  • for us to demonstrate whether the possible interaction of
  • glutamate regulation and anxiety behaviour may arise from a
  • loss of signal integrity instead of, or in addition to, abnormal
  • levels of receptor activation. Glutamate homeostatic control
  • mechanism, includes two main pathways: the cystine/
  • glutamate exchanger system xc and the glial glutamate
  • transporter EAAT2/GLT-1. Changes in the balance between
  • synaptic and extrasynaptic glutamate levels in turn influence
  • signaling through pre and postsynaptic glutamate receptors,
  • and thus affect synaptic plasticity and circuit-level activity.
  • Synchronization of cortical activity is regulated by complex
  • inter-neuronal connections (Reissner and Kalivas, 2010). Research literature indicating the role of glutamate
  • pathways of these drugs is becoming increasingly important
  • to reveal the relation between glutamate and psychiatric
  • conditions. There is a growing body of literature of potential
  • benefit of NAC and CTX in a wide range of neuropsychiatric
  • disorders (Linck et al., 2012; Alajaji et al., 2013). Further
  • preclinical efforts to define their neuropsychopharmacological
  • activity profile could be useful for more precisely defining
  • and understanding the entire therapeutic potential of these
  • drugs either used as monotherapy or in combination with
  • presently used drugs. The results of the present study suggest
  • that system xc- contributes to states of anxiety, increased
  • system xc - may represent an effective therapeutic endpoint;
  • however the specific brain region and neurotransmitter
  • system mediating these behaviours will require further investigations.
  • Chakraborti, A., Gulati, K., Ray, A., 2008. Age related differences in stress-induced neurobehavioural responses in rats: Modulation by antioxi- dants and nitrergic agents. Behav. Brain Res. Dec. 194, 86-91.
  • Chu, K., Lee, S.T., Sinn, D.I., Ko, S.Y., Kim, E.H., Kim, J.M., Kim, S.J., Park, D.K., Jung, K.H., Song, E.C., Lee, S.K., Kim, M., Roh, J.K., 2007. Pharmacological induction of ischemic tolerance by glutamate transporter-1 (EAAT2) upregulation. Stroke. 38, 177-182.
  • Cruz, A.P., Frei, F., and Graeff, F.G., 1994. Ethopharmacological analysis of rat behaviour on the elevated plus-maze, Pharmacol. Biochem. Behav. 49, 171-176.
  • Espejo, E.F., 1997. Structure of the mouse behaviour on the elevated plus-maze test of anxiety Behav. Brain Res. 86. 105-112.
  • Faludi, G., Gonda, X., Bagdy, G., Dome, P., 2012. Pharmaco- and therapygenetic aspects in the treatment of anxiety disorders beyond the sero- tonergic system: A brief review. Neuropsychopharmacol. Hung. 14, 221-229.
  • Fernandes, C., File, S.E., 1996. The influence of open arm ledges and maze experience in the elevated plus-maze. Pharmacol. Biochem. Behav. 54, 31-40.
  • File, S.E., 1992. Behavioural detection of anxiolytic action. In J.M.Elliott, D.J. Heal and C.A. Marsden (Eds.) Experimental Approachesto Anxiety and Depression. Wiley, Chichester, pp. 25-44.
  • Hogg, S., 1996. A Review of the Validity and Variability of the Elevated Plus-Maze as an Animal Model of Anxiety. Pharmacol. Biochem. Behav. 54. 21-30.
  • Holmes, A., Parmigiani, S., Ferrari, P.F., Palanza, P., Rodgers, R.J., 2000. Behavioural profile of wild mice in the elevated plus-maze test for anxiety. Physiol. Behav. 71, 509-516.
  • Karaman, I., Kizilay-Ozfidan, G., Karadag, C.H., Ulugol, A., 2013. Lack of effect of ceftriaxone, a GLT-1 transporter activator, on spatial me- mory in mice. Pharmacol. Biochem. Behav. 108, 61-65. doi: 10.1016/j.pbb.2013.04.013.
  • Kim, K., Lee, S.G., Kegelman, T.P., Su, Z.Z., Das, S.K., Dash, R., Dasgupta, S., Barral, P.M., Hedvat, M., Diaz, P., Reed, J.C., Stebbins, J.L., Pellecchia, M., Sarkar, D., Fisher, P.B., 2011. Role of excitatory amino acid transporter-2 (EAAT2) and glutamate in neurodegeneration: Opportunities for developing novel therapeutics. J. Cell Physiol. 226, 2484-2493. doi:10.1002/jcp.22609.
  • Kurt, M., Bilge, S.S., Kukula, O., Celik, S., Kesim, Y., 2003. Anxiolytic-like profile of propofol, a general anesthetic, in the plus-maze test in mice. Pol. J. Pharmacol. 55, 973-977.
  • Lewerenz, J., Albrecht, P., Tien, M.L., Henke, N., Karumbayaram, S., Kornblum, H.I., Wiedau-Pazos, M., Schubert, D., Maher, P., Methner, A., 2009. Induction of Nrf2 and xCT are involved in the action of the neuroprotective antibiotic ceftriaxone in vitro. J. Neurochem. 111, 332- 343. doi:10.1111/j.1471-4159.2009.06347.x.
  • Linck, V. M., Costa-Campos, L., Pilz, L.K., Garcia, C.R., Elisabetsky E. 2012. AMPA glutamate receptors mediate the antidepressant-like effects of N-acetylcysteine in the Mouse tail suspension test. Behav. Pharmacol. 23, 171-177. doi:10.1097/FBP.0b013e3283512c3a.
  • Lutgen, Victoria, The Contribution of System Xc-to Prefrontal Cortical Mediated Behaviours Associated with Schizophrenia (2012). Dissertati- ons (2009 -). 103-130. http://epublications.marquette.edu/dissertations_mu/176ç.
  • Macaluso, A., Bernabucci,, M., Trabucco, A., Ciolli, L., Troisi, F, Baldini, R., Gradini, R., Battaglia, G., Nicoletti, F., Collini, S., 2013. Analgesic effect of a single preoperative dose of the antibiotic ceftriaxone in humans. Pain. 14, 604-612. doi: 10.1016/j.jpain.2013.01.774.
  • Prut, L., Belzung, C., 2003. The open field as a paradigm to measure the effects of drugs on anxiety-like behaviours: A review. Eur. J. Pharmacol. 463, 3-33.
  • Ramos, A, Mormède, P., 1998. Stress and emotionality: A multidimensional and genetic approach. Neurosci. Biobehav. Rev. 22, 33-57.
  • Rebuelto, M., Ambros, L., Rubio, M., 2003. Daily variations in ceftriaxone pharmacokinetics in rats. Antimicrob. Agents Chemother. 47, 809- 812.
  • Reissner, K.J., Kalivas, P.W., 2010. Using glutamate homeostasis as a target for treating addictive disorders. Behav Pharmacol. 21, 514-522. doi: 10.1097/FBP.0b013e32833d41b2.
  • Samuni, Y., Goldstein, S., Dean, O.M., Berk, M., 2013. The chemistry and biological activities of N-acetylcysteine. Biochim Biophys Acta. Aug;1830, :4117-4129. doi:10.1016/j.bbagen.2013.04.016.
  • Trantham-Davidson, H., LaLumiere, R.T., Reissner, K.J., Kalivas, P.W., Knackstedt, L.A., 2012. Ceftriaxone normalizes nucleus accumbens synaptic transmission, glutamate transport, and export following cocaine self-administration and extinction training. J. Neurosci. 32, 12406- 12410. doi: 10.1523/JNEUROSCI.1976-12.2012.
  • Verma, R., Mishra, V., Sasmal, D., Raghubir, R., 2010. Pharmacological evaluation of glutamate transporter 1 (GLT-1) mediated neuroprotection following cerebral ischemia/reperfusion injury. Eur. J. Pharmacol. 638, 65-71. doi:10.1016/j.ejphar.2010.04.021.
  • Walsh, R.N., Cummins, R.A., 1976. The Open-Field Test: A critical review. Psychol. Bull. 83, 482-504.

Behavioural responses in rats; modulation with beta-lactam antibiotics and antioxidants

Year 2014, Volume: 31 Issue: 1, 43 - 50, 05.06.2014

Abstract

N-Acetylcysteine (NAC) has been in clinical practice for several decades as a mucolytic agent and has been used also for the treatment of paracetamol intoxication, doxorubicin- induced cardiotoxicity, stable angina pectoris, ischemia-reperfusion cardiac injury, acute respiratory distress syndrome bronchitis, chemotherapy-induced toxicity, HIV/AIDS, radio contrastinduced nephropathy, heavymetal toxicity and psychiatric disorders including schizophrenia, bipolar disorder and addiction. It has been recently shown that NAC modulates the glutamatergic system through the system xc (Cystine-Glutamate Antiporter): Antiporter cysteine/glutamate. Ceftriaxone (CTX), a β-lactam antibiotic, is also shown to led to an increase of excitatory amino-acid transporter 2 (EAAT2) expression and glutamate transport activity in the brain in animal studies. It has been demonstrated that CTX has neuroprotective effects in both in vitro and in vivo models based on its ability to inhibit neuronal cell death by preventing glutamate excitotoxicity. The aim of the present study was to investigate the neurobehavioural effects of acute administration of NAC and CTX alone and in combination in open field and elevated plus maze tests. For this aim, three different doses (50, 100 and 200 mg/kg, i.p.) of CTX and NAC alone in the first part and their combination in the second part of the experiments and two different doses of diazepam were evaluated in open field and elevated plus maze tests. 200 mg/kg of NAC revealed anxiolytic-like behaviours in both tests while CTX 200 mg/kg failed to produce. Further investigations need to be conducted to rule out the involvement of system xc- on anxiety related behaviours. Increased system xc may represent an effective therapeutic endpoint.

References

  • Alajaji, M., Bowers, M.S., Knackstedt, L., Damaj, M.I., 2013. Effects of the beta-lactam antibiotic ceftriaxone on nicotine withdrawal and nico- tine-induced reinstatement of preference in mice. Psychol. 228, 419-426. doi:10.1007/s00213-013-3047-3043.
  • Bailey, K.R., Crawley, J.N., 2009. Anxiety-Related Behaviours in Mice. In: Buccafusco, J.J., editor. Methods of behaviour analysis in neuros- cience. 2nd edition. Boca Raton (FL): CRC Press; Chapter 5, 3-27.
  • Baumann, M.H., Clark, R.D., Rothman, R.B., 2008. Locomotor stimulation produced by 3,4-methylenedioxymethamphetamine (MDMA) is cor- related with dialysate levels of serotonin and dopamine in rat brain. Pharmacol. Biochem. Behav. 90, 208-217. doi:10.1016/ j.pbb.2008.02.018.
  • Bernabucci, M., Notartomaso, S., Zappulla, C., Fazio, F., Cannella, M., Motolese, M., Battaglia, G., Bruno, V., Gradini, R., Nicoletti, F., 2012. N-Acetyl-cysteine causes analgesia by reinforcing the endogenous activation of type-2 metabotropic glutamate receptors. Mol. Pain. 23, 77. doi: 10.1186/1744-8069-8-77.
  • Bridges, R., Lutgen, V., Lobner, D., Baker, D.A., 2012. Thinking outside the cleft to understand synaptic activity: Contribution of the cys- tine-glutamate antiporter (System xc-) to normal and pathological glutamatergic signaling. Pharmacol. Rev. 64, 780-802. doi:10.1124 / pr.110.003889.
  • However, chronic use of CTX, a parenteral antibiotic, is not
  • practical for routine treatment of behavioural disorders and
  • also may change the microflora of the gut in favour of a
  • superinfection and in addition to this, concern of antibiotic
  • resistance with the repeated doses of the drug should be kept
  • in mind. Given the role of EAATs to compartmentalize
  • glutamate into functionally distinct pools (e.g., synaptic,
  • extrasynaptic), it is possible that receptors located in the
  • synapse or in the extrasynaptic compartment are being
  • stimulated by glutamate diffusing across microdomains
  • (Bridges et al., 2012). It may be a further investigation area
  • for us to demonstrate whether the possible interaction of
  • glutamate regulation and anxiety behaviour may arise from a
  • loss of signal integrity instead of, or in addition to, abnormal
  • levels of receptor activation. Glutamate homeostatic control
  • mechanism, includes two main pathways: the cystine/
  • glutamate exchanger system xc and the glial glutamate
  • transporter EAAT2/GLT-1. Changes in the balance between
  • synaptic and extrasynaptic glutamate levels in turn influence
  • signaling through pre and postsynaptic glutamate receptors,
  • and thus affect synaptic plasticity and circuit-level activity.
  • Synchronization of cortical activity is regulated by complex
  • inter-neuronal connections (Reissner and Kalivas, 2010). Research literature indicating the role of glutamate
  • pathways of these drugs is becoming increasingly important
  • to reveal the relation between glutamate and psychiatric
  • conditions. There is a growing body of literature of potential
  • benefit of NAC and CTX in a wide range of neuropsychiatric
  • disorders (Linck et al., 2012; Alajaji et al., 2013). Further
  • preclinical efforts to define their neuropsychopharmacological
  • activity profile could be useful for more precisely defining
  • and understanding the entire therapeutic potential of these
  • drugs either used as monotherapy or in combination with
  • presently used drugs. The results of the present study suggest
  • that system xc- contributes to states of anxiety, increased
  • system xc - may represent an effective therapeutic endpoint;
  • however the specific brain region and neurotransmitter
  • system mediating these behaviours will require further investigations.
  • Chakraborti, A., Gulati, K., Ray, A., 2008. Age related differences in stress-induced neurobehavioural responses in rats: Modulation by antioxi- dants and nitrergic agents. Behav. Brain Res. Dec. 194, 86-91.
  • Chu, K., Lee, S.T., Sinn, D.I., Ko, S.Y., Kim, E.H., Kim, J.M., Kim, S.J., Park, D.K., Jung, K.H., Song, E.C., Lee, S.K., Kim, M., Roh, J.K., 2007. Pharmacological induction of ischemic tolerance by glutamate transporter-1 (EAAT2) upregulation. Stroke. 38, 177-182.
  • Cruz, A.P., Frei, F., and Graeff, F.G., 1994. Ethopharmacological analysis of rat behaviour on the elevated plus-maze, Pharmacol. Biochem. Behav. 49, 171-176.
  • Espejo, E.F., 1997. Structure of the mouse behaviour on the elevated plus-maze test of anxiety Behav. Brain Res. 86. 105-112.
  • Faludi, G., Gonda, X., Bagdy, G., Dome, P., 2012. Pharmaco- and therapygenetic aspects in the treatment of anxiety disorders beyond the sero- tonergic system: A brief review. Neuropsychopharmacol. Hung. 14, 221-229.
  • Fernandes, C., File, S.E., 1996. The influence of open arm ledges and maze experience in the elevated plus-maze. Pharmacol. Biochem. Behav. 54, 31-40.
  • File, S.E., 1992. Behavioural detection of anxiolytic action. In J.M.Elliott, D.J. Heal and C.A. Marsden (Eds.) Experimental Approachesto Anxiety and Depression. Wiley, Chichester, pp. 25-44.
  • Hogg, S., 1996. A Review of the Validity and Variability of the Elevated Plus-Maze as an Animal Model of Anxiety. Pharmacol. Biochem. Behav. 54. 21-30.
  • Holmes, A., Parmigiani, S., Ferrari, P.F., Palanza, P., Rodgers, R.J., 2000. Behavioural profile of wild mice in the elevated plus-maze test for anxiety. Physiol. Behav. 71, 509-516.
  • Karaman, I., Kizilay-Ozfidan, G., Karadag, C.H., Ulugol, A., 2013. Lack of effect of ceftriaxone, a GLT-1 transporter activator, on spatial me- mory in mice. Pharmacol. Biochem. Behav. 108, 61-65. doi: 10.1016/j.pbb.2013.04.013.
  • Kim, K., Lee, S.G., Kegelman, T.P., Su, Z.Z., Das, S.K., Dash, R., Dasgupta, S., Barral, P.M., Hedvat, M., Diaz, P., Reed, J.C., Stebbins, J.L., Pellecchia, M., Sarkar, D., Fisher, P.B., 2011. Role of excitatory amino acid transporter-2 (EAAT2) and glutamate in neurodegeneration: Opportunities for developing novel therapeutics. J. Cell Physiol. 226, 2484-2493. doi:10.1002/jcp.22609.
  • Kurt, M., Bilge, S.S., Kukula, O., Celik, S., Kesim, Y., 2003. Anxiolytic-like profile of propofol, a general anesthetic, in the plus-maze test in mice. Pol. J. Pharmacol. 55, 973-977.
  • Lewerenz, J., Albrecht, P., Tien, M.L., Henke, N., Karumbayaram, S., Kornblum, H.I., Wiedau-Pazos, M., Schubert, D., Maher, P., Methner, A., 2009. Induction of Nrf2 and xCT are involved in the action of the neuroprotective antibiotic ceftriaxone in vitro. J. Neurochem. 111, 332- 343. doi:10.1111/j.1471-4159.2009.06347.x.
  • Linck, V. M., Costa-Campos, L., Pilz, L.K., Garcia, C.R., Elisabetsky E. 2012. AMPA glutamate receptors mediate the antidepressant-like effects of N-acetylcysteine in the Mouse tail suspension test. Behav. Pharmacol. 23, 171-177. doi:10.1097/FBP.0b013e3283512c3a.
  • Lutgen, Victoria, The Contribution of System Xc-to Prefrontal Cortical Mediated Behaviours Associated with Schizophrenia (2012). Dissertati- ons (2009 -). 103-130. http://epublications.marquette.edu/dissertations_mu/176ç.
  • Macaluso, A., Bernabucci,, M., Trabucco, A., Ciolli, L., Troisi, F, Baldini, R., Gradini, R., Battaglia, G., Nicoletti, F., Collini, S., 2013. Analgesic effect of a single preoperative dose of the antibiotic ceftriaxone in humans. Pain. 14, 604-612. doi: 10.1016/j.jpain.2013.01.774.
  • Prut, L., Belzung, C., 2003. The open field as a paradigm to measure the effects of drugs on anxiety-like behaviours: A review. Eur. J. Pharmacol. 463, 3-33.
  • Ramos, A, Mormède, P., 1998. Stress and emotionality: A multidimensional and genetic approach. Neurosci. Biobehav. Rev. 22, 33-57.
  • Rebuelto, M., Ambros, L., Rubio, M., 2003. Daily variations in ceftriaxone pharmacokinetics in rats. Antimicrob. Agents Chemother. 47, 809- 812.
  • Reissner, K.J., Kalivas, P.W., 2010. Using glutamate homeostasis as a target for treating addictive disorders. Behav Pharmacol. 21, 514-522. doi: 10.1097/FBP.0b013e32833d41b2.
  • Samuni, Y., Goldstein, S., Dean, O.M., Berk, M., 2013. The chemistry and biological activities of N-acetylcysteine. Biochim Biophys Acta. Aug;1830, :4117-4129. doi:10.1016/j.bbagen.2013.04.016.
  • Trantham-Davidson, H., LaLumiere, R.T., Reissner, K.J., Kalivas, P.W., Knackstedt, L.A., 2012. Ceftriaxone normalizes nucleus accumbens synaptic transmission, glutamate transport, and export following cocaine self-administration and extinction training. J. Neurosci. 32, 12406- 12410. doi: 10.1523/JNEUROSCI.1976-12.2012.
  • Verma, R., Mishra, V., Sasmal, D., Raghubir, R., 2010. Pharmacological evaluation of glutamate transporter 1 (GLT-1) mediated neuroprotection following cerebral ischemia/reperfusion injury. Eur. J. Pharmacol. 638, 65-71. doi:10.1016/j.ejphar.2010.04.021.
  • Walsh, R.N., Cummins, R.A., 1976. The Open-Field Test: A critical review. Psychol. Bull. 83, 482-504.
There are 66 citations in total.

Details

Primary Language English
Subjects Health Care Administration
Journal Section Basic Medical Sciences
Authors

Evren Şavlı

Publication Date June 5, 2014
Submission Date December 8, 2013
Published in Issue Year 2014 Volume: 31 Issue: 1

Cite

APA Şavlı, E. (2014). Behavioural responses in rats; modulation with beta-lactam antibiotics and antioxidants. Journal of Experimental and Clinical Medicine, 31(1), 43-50.
AMA Şavlı E. Behavioural responses in rats; modulation with beta-lactam antibiotics and antioxidants. J. Exp. Clin. Med. June 2014;31(1):43-50.
Chicago Şavlı, Evren. “Behavioural Responses in Rats; Modulation With Beta-Lactam Antibiotics and Antioxidants”. Journal of Experimental and Clinical Medicine 31, no. 1 (June 2014): 43-50.
EndNote Şavlı E (June 1, 2014) Behavioural responses in rats; modulation with beta-lactam antibiotics and antioxidants. Journal of Experimental and Clinical Medicine 31 1 43–50.
IEEE E. Şavlı, “Behavioural responses in rats; modulation with beta-lactam antibiotics and antioxidants”, J. Exp. Clin. Med., vol. 31, no. 1, pp. 43–50, 2014.
ISNAD Şavlı, Evren. “Behavioural Responses in Rats; Modulation With Beta-Lactam Antibiotics and Antioxidants”. Journal of Experimental and Clinical Medicine 31/1 (June 2014), 43-50.
JAMA Şavlı E. Behavioural responses in rats; modulation with beta-lactam antibiotics and antioxidants. J. Exp. Clin. Med. 2014;31:43–50.
MLA Şavlı, Evren. “Behavioural Responses in Rats; Modulation With Beta-Lactam Antibiotics and Antioxidants”. Journal of Experimental and Clinical Medicine, vol. 31, no. 1, 2014, pp. 43-50.
Vancouver Şavlı E. Behavioural responses in rats; modulation with beta-lactam antibiotics and antioxidants. J. Exp. Clin. Med. 2014;31(1):43-50.