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Effects of ceftriaxone on ethanol intake: a possible role for xCT and GLT-1 isoforms modulation of glutamate levels in P rats.
Psychopharmacology (Berl) 2014; 231(20):4049-57P

Abstract

RATIONALE

Evidence suggests that glutamate transporter 1 (GLT-1) and cystine/glutamate exchanger transporter (xCT) are critical in maintaining glutamate homeostasis. We have recently demonstrated that ceftriaxone treatment induced upregulation of GLT1 levels and attenuated ethanol intake; however, less is known about the involvement of xCT on ethanol intake. In this study, we investigated the effects of ceftriaxone on the levels of xCT in both continuous and relapse-like ethanol drinking, as well as GLT-1 isoforms, and glutamate aspartate transporter (GLAST) in relapse-like ethanol intake.

METHODS

P rats received free choice of 15 and 30 % ethanol and water for 5 weeks and then deprived of ethanol for 2 weeks. Rats were treated with ceftriaxone (100 mg/kg, i.p.) or saline during the last 5 days of the 2-week deprivation period. After deprivation period, P rats were re-exposed to free choice of 15 and 30 % ethanol and water for nine consecutive days. A second group of P rats was given continuous ethanol access for 5 weeks, then ceftriaxone (100 mg/kg, i.p.) or saline throughout the week 6.

RESULTS

Ceftriaxone significantly attenuated relapse-like ethanol intake. Importantly, this effect of ceftriaxone was associated in part with upregulation of the levels of GLT-1a and GLT-1b isoforms and xCT in the prefrontal cortex (PFC) and the nucleus accumbens (NAc). There were no significant differences in GLAST expression among all groups. We also found that ceftriaxone treatment increased xCT levels in both PFC and NAc in continuous ethanol intake.

CONCLUSION

These findings suggest that xCT and GLT-1 isoforms might be target proteins for the treatment of alcohol dependence.

Authors+Show Affiliations

Department of Pharmacology, College of Pharmacy and Pharmaceutical Sciences, University of Toledo, Health Science Campus, 3000 Arlington Avenue, Toledo, OH, 43614, USA.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

24687412

Citation

Alhaddad, Hasan, et al. "Effects of Ceftriaxone On Ethanol Intake: a Possible Role for xCT and GLT-1 Isoforms Modulation of Glutamate Levels in P Rats." Psychopharmacology, vol. 231, no. 20, 2014, pp. 4049-57.
Alhaddad H, Das SC, Sari Y. Effects of ceftriaxone on ethanol intake: a possible role for xCT and GLT-1 isoforms modulation of glutamate levels in P rats. Psychopharmacology (Berl). 2014;231(20):4049-57.
Alhaddad, H., Das, S. C., & Sari, Y. (2014). Effects of ceftriaxone on ethanol intake: a possible role for xCT and GLT-1 isoforms modulation of glutamate levels in P rats. Psychopharmacology, 231(20), pp. 4049-57. doi:10.1007/s00213-014-3545-y.
Alhaddad H, Das SC, Sari Y. Effects of Ceftriaxone On Ethanol Intake: a Possible Role for xCT and GLT-1 Isoforms Modulation of Glutamate Levels in P Rats. Psychopharmacology (Berl). 2014;231(20):4049-57. PubMed PMID: 24687412.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effects of ceftriaxone on ethanol intake: a possible role for xCT and GLT-1 isoforms modulation of glutamate levels in P rats. AU - Alhaddad,Hasan, AU - Das,Sujan C, AU - Sari,Youssef, Y1 - 2014/04/01/ PY - 2013/05/17/received PY - 2014/03/12/accepted PY - 2014/4/2/entrez PY - 2014/4/2/pubmed PY - 2015/10/13/medline SP - 4049 EP - 57 JF - Psychopharmacology JO - Psychopharmacology (Berl.) VL - 231 IS - 20 N2 - RATIONALE: Evidence suggests that glutamate transporter 1 (GLT-1) and cystine/glutamate exchanger transporter (xCT) are critical in maintaining glutamate homeostasis. We have recently demonstrated that ceftriaxone treatment induced upregulation of GLT1 levels and attenuated ethanol intake; however, less is known about the involvement of xCT on ethanol intake. In this study, we investigated the effects of ceftriaxone on the levels of xCT in both continuous and relapse-like ethanol drinking, as well as GLT-1 isoforms, and glutamate aspartate transporter (GLAST) in relapse-like ethanol intake. METHODS: P rats received free choice of 15 and 30 % ethanol and water for 5 weeks and then deprived of ethanol for 2 weeks. Rats were treated with ceftriaxone (100 mg/kg, i.p.) or saline during the last 5 days of the 2-week deprivation period. After deprivation period, P rats were re-exposed to free choice of 15 and 30 % ethanol and water for nine consecutive days. A second group of P rats was given continuous ethanol access for 5 weeks, then ceftriaxone (100 mg/kg, i.p.) or saline throughout the week 6. RESULTS: Ceftriaxone significantly attenuated relapse-like ethanol intake. Importantly, this effect of ceftriaxone was associated in part with upregulation of the levels of GLT-1a and GLT-1b isoforms and xCT in the prefrontal cortex (PFC) and the nucleus accumbens (NAc). There were no significant differences in GLAST expression among all groups. We also found that ceftriaxone treatment increased xCT levels in both PFC and NAc in continuous ethanol intake. CONCLUSION: These findings suggest that xCT and GLT-1 isoforms might be target proteins for the treatment of alcohol dependence. SN - 1432-2072 UR - https://www.unboundmedicine.com/medline/citation/24687412/Effects_of_ceftriaxone_on_ethanol_intake:_a_possible_role_for_xCT_and_GLT_1_isoforms_modulation_of_glutamate_levels_in_P_rats_ L2 - https://dx.doi.org/10.1007/s00213-014-3545-y DB - PRIME DP - Unbound Medicine ER -