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Activation of GABAA receptors in the medial prefrontal cortex produces an anxiolytic-like response

Published online by Cambridge University Press:  08 March 2013

Jalal Solati ,
Ramin Hajikhani  and
Yulia Golub
Jalal Solati
Affiliation:
Department of Biology, Karaj branch, Islamic Azad University, Karaj, Iran
Ramin Hajikhani
Affiliation:
Department of Biology, Karaj branch, Islamic Azad University, Karaj, Iran
Yulia Golub*
Affiliation:
Department of Child and Adolescent Mental Health, University of Erlangen-Nuremberg
*
Jalal Solati, Department of Biology, School of Science, Karaj Branch, Islamic Azad University, Karaj, Iran. Tel: +98261 4418143; Fax: +98261 4418156; E-mail solati@kiau.ac.ir;
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Abstract

Objectives

There has been increasing evidence that the γ-aminobutyric acid (GABA)ergic system is involved in the neurobiology of anxiety. The present study aimed to investigate the role of GABAergic systems in the modulation of anxiety in the medial prefrontal cortex (mPFC) of rats using the elevated plus maze test.

Methods

Rats were anaesthetised with a mixture of ketamine and xylazine, and then special cannulae were inserted stereotaxically into the mPFC. After 5–7 days of recovery, the effects of intra-mPFC administration of GABAergic agents were studied.

Results

Bilateral injection of the GABAA receptor agonist muscimol (0.25, 0.5 and 1 μg/rat) produces an anxiolytic-like effect, shown by significant increases in the percentage of open-arm time (%OAT) and percentage of open-arm entries (%OAE). Intra-mPFC administration of the GABAA receptor antagonist bicuculline (0.25, 0.5 and 1 μg/rat) produces significant anxiogenic-like behaviour. However, intra-mPFC injection of the GABAB receptor agonist baclofen (0.05, 0.1 and 0.2 μg/rat) and the GABAB receptor antagonist CGP35348 (5, 10 and 15 μg/rat) did not alter %OAT and %OAE significantly.

Conclusion

The results of the present study demonstrate that the GABAergic system of the mPFC modulates anxiety-related behaviours of rats through GABAA receptors.

Keywords

anxietyGABAmedial prefrontal cortex
Type
Original Articles
Information
Acta Neuropsychiatrica , Volume 25 , Issue 4 , August 2013 , pp. 221 - 226
Copyright
Copyright © Scandinavian College of Neuropsychopharmacology 2013 

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References

1.George, O, Koob, GF. Individual differences in prefrontal cortex function and the transition from drug use to drug dependence. Neurosci Biobeh Rev 2010;35:232–247.CrossRefGoogle ScholarPubMed
2.Yan, Z. Regulation of GABAergic inhibition by serotonin signaling in prefrontal cortex. Mol Neurobiol 2002;26:203–216.Google Scholar
3.Jinks, AL, McGregor, IS. Modulation of anxiety-related behaviours following lesions of the prelimbic or infralimbic cortex in the rat. Brain Res 1997;772:181–190.Google Scholar
4.Monk, C, Nelson, E, McClure, Eet al. Ventrolateral prefrontal cortex activation and attentional bias in response to angry faces in adolescents with generalized anxiety disorder. Amer J Psychiatry 2006;163:1091–1097.Google Scholar
5.Tsutsui, K, Ukena, K, Usui, M, Sakamoto, H, Takase, M. Novel brain function: biosynthesis and actions of neurosteroids in neurons. Neuroscience Res 2000;36:261–273.CrossRefGoogle ScholarPubMed
6.Hasler, G, van der Veen, JW, Grillon, C, Drevets, WC, Shen, J. Effect of acute psychological stress on prefrontal GABA concentration determined by proton magnetic resonance spectroscopy. Amer J psychiatry 2010;167:1226–1231.Google Scholar
7.Shekhar, A. GABA receptors in the region of the dorsomedial hypothalamus of rats regulate anxiety in the elevated plus-maze test. I. Behavioral measures. Brain res 1993;627:9–16.Google Scholar
8.Hirani, K, Sharma, AN, Jain, NS, Ugale, RR, Chopde, CT. Evaluation of GABAergic neuroactive steroid 3α-hydroxy-5α-pregnane-20-one as a neurobiological substrate for the anti-anxiety effect of ethanol in rats. Psychopharmacology 2005;180:267–278.Google Scholar
9.Zarrindast, MR, Solati, J, Oryan, S, Parivar, K. Effect of intra-amygdala injection of nicotine and GABA receptor agents on anxiety-like behaviour in rats. Pharmacology 2008;82:276–284.Google Scholar
10.Carr, DB, Sesack, SR. GABA-containing neurons in the rat ventral tegmental area project to the prefrontal cortex. Synapse 2000;38:114–123.Google Scholar
11.Torregrossa, MM, Tang, XC, Kalivas, PW. The glutamatergic projection from the prefrontal cortex to the nucleus accumbens core is required for cocaine-induced decreases in ventral pallidal GABA. Neurosci Let 2008;438:142–145.Google Scholar
12.Simpson, J, Drevets, W, Snyder, A, Gusnard, D, Raichle, M. Emotion-induced changes in human medial prefrontal cortex: II. During anticipatory anxiety. Proc Natl Acad Sci USA 2001;98:688–693.Google Scholar
13.Lacroix, L, White, I, Feldon, J. Effect of excitotoxic lesions of rat medial prefrontal cortex on spatial memory. Behav Brain Res 2002;133:69–81.Google Scholar
14.Paxinos, G, Watson, C. The rat brain in stereotaxic coordinates. Amsterdam: Elsevier, 2007.Google Scholar
15.Solati, J, Salari, AA, Bakhtiari, A. 5HT 1A and 5HT 1B receptors of medial prefrontal cortex modulate anxiogenic-like behaviors in rats. Neurosci Let 2011;504:325–329.Google Scholar
16.Solati, J. Dorsal hippocampal N-methyl-d-aspartate glutamatergic and [delta]-opioidergic systems modulate anxiety behaviors in rats in a noninteractive manner. Kaohsiung J Med Sci 2011;27:485–493.Google Scholar
17.Solati, J, Zarrindast, M, Salari, A. Dorsal hippocampal opioidergic system modulates anxiety-like behaviors in adult male Wistar rats. Psychiatry Clin Neurosci 2010;634–641.Google Scholar
18.Solati, J, Salari, A. Involvement of dorsal hippocampal NMDA-glutamatergic system in anxiety-related behaviors of rats. Neurochemical J 2011;5:194–199.CrossRefGoogle Scholar
19.Kalueff, AV, Nutt, DJ. Role of GABA in anxiety and depression. Depress Anxiety 2007;24:495–517.CrossRefGoogle ScholarPubMed
20.Tasan, RO, Bukovac, A, Peterschmitt, YNet al. Altered GABA transmission in a mouse model of increased trait anxiety. Neuroscience 2011;183:71–80.Google Scholar
21.Matsumoto, M, Togashi, H, Kaku, A, Kanno, M, Tahara, K, Yoshioka, M. Cortical GABAergic regulation of dopaminergic responses to psychological stress in the rat dorsolateral striatum. Synapse 2005;56:117–121.Google Scholar
22.Depino, AM, Tsetsenis, T, Gross, C. GABA homeostasis contributes to the developmental programming of anxiety-related behavior. Brain Res 2008;1210:189–199.Google Scholar
23.Kalueff, A, Nutt, D. Role of GABA in memory and anxiety. Depress Anxiety 1996;4:100–110.Google Scholar
24.Ågmo, A, Pruneda, R, Guzmán, M, Gutiérrez, M. GABAergic drugs and conflict behavior in the rat: lack of similarities with the actions of benzodiazepines. Naunyn-Schmiedebergs Arch Pharmacol 1991;344:314–322.Google Scholar
25.Dalvi, A, Rodgers, R. GABAergic influences on plus-maze behaviour in mice. Psychopharmacology 1996;128:380–397.Google Scholar
26.Hodge, CW, Raber, J, McMahon, Tet al. Decreased anxiety-like behavior, reduced stress hormones, and neurosteroid supersensitivity in mice lacking protein kinase Cepsilon. J Clin Invest 2002;110:1003–1010.Google Scholar
27.Sanders, S, Shekhar, A. Regulation of anxiety by GABAA receptors in the rat amygdala. Pharmacol Biochem Behav 1995;52:701–706.Google Scholar
28.Lewis, DA. GABAergic local circuit neurons and prefrontal cortical dysfunction in schizophrenia. Brain Res Rev 2000;31:270–276.CrossRefGoogle ScholarPubMed
29.Hashimoto, T, Arion, D, Unger, Tet al. Alterations in GABA-related transcriptome in the dorsolateral prefrontal cortex of subjects with schizophrenia. Mol Psychiatry 2007;13:147–161.Google Scholar
30.Nair-Roberts, R, Chatelain-Badie, S, Benson, E, White-Cooper, H, Bolam, J, Ungless, M. Stereological estimates of dopaminergic, GABAergic and glutamatergic neurons in the ventral tegmental area, substantia nigra and retrorubral field in the rat. Neuroscience 2008;152:1024–1031.Google Scholar
31.Monk, CS, Telzer, EH, Mogg, Ket al. Amygdala and ventrolateral prefrontal cortex activation to masked angry faces in children and adolescents with generalized anxiety disorder. Arch Gen Psychiatry 2008;65:568–576.Google Scholar