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Gender specific influence of endogenous glutamate release on stress-induced fear in rats.
Endocr Regul. 2011 Jan; 45(1):13-21.ER

Abstract

OBJECTIVE

Stress, fear and anxiety are among major public health concerns. The role of glutamate in these processes is becoming more recognized with promising new drug targets. The aim of this study was to establish the gender specificity of a possible treatment of fear by glutamate antagonists in correspondence with changes in stress-hormone release.

METHODS

Footshock-induced fear was used as an anxiogenic situation in rats. A combination of two ionotrop receptor antagonists such as MK-801 (dizocilpine; 0.2 mg/kg) for NMDA (N-methyl-D-aspartic acid) and GYKI 52466 (benzodiazepine derivative; 10 mg/kg) for AMPA/kainate receptors were used for 5 days following the hypothesis that they potentiate each other the main action, but at the same time the side effects may be minimized.

RESULTS

Female rats tried to avoid the electrical stimulus more actively than males, as they spent more time with exploration and jumping and less time with freezing or rest. Ionotropic glutamate receptor antagonists have anxiolytic action. MK-801 was more effective in females, as it prevented the footshock-induced freezing per se, while in males it was effective only in combination with GyKI 52466. The locomotor side effect of MK-801 was not visible after repeated administration. The freezing behavior was positively correlated with the changes in prolactin but not with adrenocorticotropin levels.

CONCLUSIONS

We proved the involvement of endogenous glutamate neurotransmission in stress-induced fear. Therapeutical usage may involve a combination of different receptor antagonists. Special attention should be paid to the gender, as females seem to be more sensitive, therefore they require smaller doses. During the treatment the prolactin levels should be monitored.

Authors+Show Affiliations

Department of Zoology, Dr. H. S. Gour University, Sagar, India. subjain@gmail.comNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article

Language

eng

PubMed ID

21314206

Citation

Jain, S K., and D Zelena. "Gender Specific Influence of Endogenous Glutamate Release On Stress-induced Fear in Rats." Endocrine Regulations, vol. 45, no. 1, 2011, pp. 13-21.
Jain SK, Zelena D. Gender specific influence of endogenous glutamate release on stress-induced fear in rats. Endocr Regul. 2011;45(1):13-21.
Jain, S. K., & Zelena, D. (2011). Gender specific influence of endogenous glutamate release on stress-induced fear in rats. Endocrine Regulations, 45(1), 13-21.
Jain SK, Zelena D. Gender Specific Influence of Endogenous Glutamate Release On Stress-induced Fear in Rats. Endocr Regul. 2011;45(1):13-21. PubMed PMID: 21314206.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Gender specific influence of endogenous glutamate release on stress-induced fear in rats. AU - Jain,S K, AU - Zelena,D, PY - 2011/2/15/entrez PY - 2011/2/15/pubmed PY - 2011/7/23/medline SP - 13 EP - 21 JF - Endocrine regulations JO - Endocr Regul VL - 45 IS - 1 N2 - OBJECTIVE: Stress, fear and anxiety are among major public health concerns. The role of glutamate in these processes is becoming more recognized with promising new drug targets. The aim of this study was to establish the gender specificity of a possible treatment of fear by glutamate antagonists in correspondence with changes in stress-hormone release. METHODS: Footshock-induced fear was used as an anxiogenic situation in rats. A combination of two ionotrop receptor antagonists such as MK-801 (dizocilpine; 0.2 mg/kg) for NMDA (N-methyl-D-aspartic acid) and GYKI 52466 (benzodiazepine derivative; 10 mg/kg) for AMPA/kainate receptors were used for 5 days following the hypothesis that they potentiate each other the main action, but at the same time the side effects may be minimized. RESULTS: Female rats tried to avoid the electrical stimulus more actively than males, as they spent more time with exploration and jumping and less time with freezing or rest. Ionotropic glutamate receptor antagonists have anxiolytic action. MK-801 was more effective in females, as it prevented the footshock-induced freezing per se, while in males it was effective only in combination with GyKI 52466. The locomotor side effect of MK-801 was not visible after repeated administration. The freezing behavior was positively correlated with the changes in prolactin but not with adrenocorticotropin levels. CONCLUSIONS: We proved the involvement of endogenous glutamate neurotransmission in stress-induced fear. Therapeutical usage may involve a combination of different receptor antagonists. Special attention should be paid to the gender, as females seem to be more sensitive, therefore they require smaller doses. During the treatment the prolactin levels should be monitored. SN - 1210-0668 UR - https://www.unboundmedicine.com/medline/citation/21314206/Gender_specific_influence_of_endogenous_glutamate_release_on_stress_induced_fear_in_rats_ L2 - http://www.aepress.sk/_downloads/dl.php?from=pubmed&journal=ER&file=2011_01_13.pdf DB - PRIME DP - Unbound Medicine ER -