Involvement of lateral septum GABAA receptors in the regulation of anxiety-like behaviors in hemiparkinsonian rats

doi:10.12092/j.issn.1009-2501.2018.07.003

Abstract

Abstract:

AIM: To investigate the role of GABA_A receptors in the lateral septum (LS) in the regulation of anxiety-like behaviors in hemiparkinsonian rats. METHODS: A total of 167 rats were randomly divided into sham-operated group (n=85) and medial forebrain bundle (MFB) lesioned group (n=82). The open field and elevated plus maze (EPM) test were performed to study the influence of MFB lesion and intra-LS injection of GABAA agonist muscimol (0.2, 0.4 or 0.8 μg/rat) and antagonist picrotoxin (0.1, 0.2 or 0.4 μg/rat) on anxiety-like behaviors. Changes of monoamine levels in limbic related brain regions were observed by high performance liquid chromatography with electrochemical detection. RESULTS: Compared with sham-operated group, the MFB lesioned group induced anxiety-like behaviors. The dopamine (DA) levels in LS, amygdala and ventral hippocampus (vHip) were significantly decreased compared with sham-opreated group. Compared with the rats treated with vehicle in the same group, the intra-injection of muscimol in LS induced or aggravated the anxiety-like behaviors in two groups, and decreased DA and 5-hydroxytryptamine (5-HT) levels in three brain regions. In contrast, the administration of picrotoxin improved anxiety-like behaviors, and increased 5-HT in three brain regions and DA in amygdala and vHip. However, the doses producing the behavioral effects in the lesioned rats were higher than those in sham-operated rats. CONCLUSION: GABA_A receptors in the LS are involved in the regulation of anxiety-like behaveiors, which is attributable to changes in dopamine, 5-HT levels in the limbic-related brain regions after activation and blockade of GABA_A receptors.

Key words: lateral septum, GABA_A receptors, anxiety, Parkinson's disease

CLC Number:

R965.2

CHANG Yongli, WANG Chunlei, YUAN Li, GUO Xiaoshu, HAN Lingna. Involvement of lateral septum GABAA receptors in the regulation of anxiety-like behaviors in hemiparkinsonian rats[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2018, 23(7): 734-742.

References

［1］Mongeau R, Miller GA, Chiang E, et al. Neural correlates of competing fear behaviors evoked by an innately aversive stimulus［J］. J Neurosci, 2003, 23(9): 3855-3868.

［2］Salome N, Salchner P, Viltart O, et al. Neurobiological correlates of high (HAB) versus low anxiety-related behavior (LAB): differential Fos expression in HAB and LAB rats［J］. Biol Psychiatry, 2004, 55(7): 715-723.

［3］Singewald N, Salchner P, Sharp T. Induction of c-Fos expression in specific areas of the fear circuitry in rat forebrain by anxiogenic drugs［J］. Biol Psychiatry, 2003, 53: 275-283.

［4］Yadin E, Thomas E, Grishkat HL, et al. The role of the lateral septum in anxiolysis［J］. Physiol Behav, 1993, 53(4): 1077-1083.

［5］Menard J, Treit D. Lateral and medial septal lesions reduce anxiety in the plus-maze and probe-burying tests［J］. Physiol Behav, 1996, 60(3): 845-853.

［6］Degroot A, Kashluba S, Treit D. Septal GABAergic and hippocampal cholinergic systems modulate anxiety in the plus-maze and shock-probe tests［J］. Pharmacol Biochem Behav, 2001, 69(3/4): 391-399.

［7］Sheehan TP, Chambers RA, Russell DS. Regulation of affect by the lateral septum: implications for neuropsychiatry［J］. Brain Res Brain Res Rev, 2004, 46(1): 71-117.

［8］Luscher B, Shen Q, Sahir N. The GABAergic deficit hypothesis of major depressive disorder［J］. Mol Psychiatry, 2011, 16(4): 383-406.

［9］Shulman LM, Taback RL, Bean J, et al. Comorbidity of the nonmotor symptoms of Parkinson's disease［J］. Mov Disord, 2001, 16(3): 507-510.

［10］Segovia J, Armstrong DM, Benzing WC, et al. Striatal glutamic acid decarboxylase immunoreactivity is increased after dopaminergic deafferentation: densitometric analysis［J］. Neurosci Lett, 1991, 122(2): 252-256.

［11］Soghomonian JJ, Laprade N. Glutamate decarboxylase (GAD67 and GAD65) gene expression is increased in a subpopulation of neurons in the putamen of Parkinsonian monkeys［J］. Synapse, 1997, 27(2): 122-132.

［12］Emir UE, Tuite PJ, Oz G. Elevated pontine and putamenal GABA levels in mild-moderate Parkinson disease detected by 7 tesla proton MRS［J］. Plos One, 2012, 7(1): e30918.

［13］Calon F, Goulet M, Blanchet PJ, et al. Levodopa or D2 agonist induced dyskinesia in MPTP monkeys: correlation with changes in dopamine and GABAA receptors in the striatopallidal complex［J］. Brain Res, 1995, 680(1/2): 43-52.

［14］Bueno CH, Zangrossi H, Jr. Nogueira RL, et al. Panicolytic-like effect induced by the stimulation of GABAA and GABAB receptors in the dorsal periaqueductal grey of rats［J］. Eur J Pharmacol, 2005, 516(3): 239-246.

［15］Shin R, Ikemoto S. Administration of the GABAA receptor antagonist picrotoxin into rat supramammillary nucleus induces c-Fos in reward-related brain structures. Supramammillary picrotoxin and c-Fos expression［J］. BMC neuroscience, 2010, 11: 101.

［16］Paxinos G, Watson C. The rat brain in stereotaxic coordinates［M］. San Diego: Academic Press, 1998.

［17］Tadaiesky MT, Dombrowski PA, Figueiredo CP, et al. Emotional, cognitive and neurochemical alterations in a premotor stage model of Parkinson's disease［J］. Neuroscience, 2008, 156(4): 830-840.

［18］Estanislau C, Ramos AC, Ferraresi PD, et al. Individual differences in the elevated plus-maze and the forced swim test［J］. Behav Processes, 2011, 86(1): 46-51.

［19］Gui ZH, Zhang QJ, Liu J, et al. Unilateral lesion of the nigrostriatal pathway decreases the response of fast-spiking interneurons in the medial prefrontal cortex to 5-HT1A receptor agonist and expression of the receptor in parvalbumin-positive neurons in the rat［J］. Neurochem Int, 2011, 59(5): 618-627.

［20］Zhang YM, Zhang L, Wang Y, et al. Activation and blockade of prelimbic 5-HT6 receptors produce different effects on depressive-like behaviors in unilateral 6-hydroxydopamine-induced Parkinson's rats［J］. Neuropharmacol, 2016, 110(ptA): 25-36.

［21］Eskow Jaunarajs KL, George JA, Bishop C. L-DOPA-induced dysregulation of extrastriatal dopamine and serotonin and affective symptoms in a bilateral rat model of Parkinson's disease［J］. Neuroscience, 2012, 218: 243-256.

［22］Eskow Jaunarajs KL, Dupre KB, Ostock CY, et al. Behavioral and neurochemical effects of chronic L-DOPA treatment on nonmotor sequelae in the hemiparkinsonian rat［J］. Behav Pharmacol, 2010, 21(7): 627-637.

［23］Jungnickel J, Kalve I, Reimers L, et al. Topology of intrastriatal dopaminergic grafts determines functional and emotional outcome in neurotoxin-lesioned rats［J］. Behav Brain Res, 2011, 216(1): 129-135.

［24］Zhang T, Chen T, Chen P, et al. MPTP-induced dopamine depletion in basolateral amygdala via decrease of D2R activation suppresses GABAA receptors expression and LTD induction leading to anxiety-like behaviors［J］. Front Mol Neurosci, 2017, 10: 247.

［25］Vega-Quiroga I, Yarur HE, Gysling K. Lateral septum stimulation disinhibits dopaminergic neurons in the antero-ventral region of the ventral tegmental area: Role of GABAA alpha 1 receptors［J］. Neuropharmacol, 2018, 128: 76-85.

［26］Thomas E, Dewolfe M, Sancar F, et al. Electrophysiological analysis of the interaction between the lateral septum and the central nucleus of the amygdala［J］. Neurosci Lett, 2012, 524(2): 79-83.

［27］Luo XM, Yuan SN, Guan XT, et al. Juvenile stress affects anxiety-like behavior and limbic monoamines in adult rats［J］. Physiol Behav, 2014, 135: 7-16.

［28］Ressler KJ, Nemeroff CB. Role of serotonergic and noradrenergic systems in the pathophysiology of depression and anxiety disorders［J］. Depress Anxiety, 2000, 12(Suppl 1): 2-19.

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