title: CXCL12 impairs the acquisition and extinction of auditory fear conditioning in rats via crosstalk with GABAergic system.
abstract: Chemokines, such as CXCL12, are signaling molecules playing an important role in immune regulations. Chemokine upsurge has also been associated with neuroinflammatory conditions characterized with cognitive impairments. Recently, some in-vitro data suggests that CXCL12 is a potential neuromodulator and interacts with GABAergic system, but, so far, whether these effects translate into alterations in neural and behavioral functions has not been investigated.
  
  
  
  In the present study, we used auditory fear conditioning as a model to define the contribution of CXCL12/CXCR4 on fear-related cognitive disorders. We microinjected different dosages of CXCL12 into the bilateral amygdala of rats to investigate their behavioral effects on the acquisition and extinction of conditioned fear memory. Moreover, we pretreated the rats with the selective CXCR4 receptor antagonist (AMD3100), GABAA antagonist (bicuculline) and GABAB antagonist (CGP55845) to examine whether the CXCL12 induced changes could be reversed.
  
  
  
  We found that intra-amygdala infusion of CXCL12 impaired the acquisition and extinction of conditioned fear response. Pretreatment with AMD3100, rescued the CXCL12 induced impairments, indicating that CXCL12 produced the effects by activating CXCR4 receptors. Furthermore, both bicuculline and CGP55845 prevented CXCL12 from impairing the rat's ability of conditioned learning, indicating a crosstalk between CXCL12/CXCR4 and GABAergic system.
  
  
  
  Our data suggest that the chemokine CXCL12 is able to regulate neurotransmitter mechanisms involved in associative learning functions, and the effect of GABAergic agents on CXCL12/CXCR4 may be new therapeutic potentials for neuroinflammatory diseases.
authors.affiliation: Department of Physiology, China Medical University, Shenyang 110001, People's Republic of China.
authors.forename: Lijuan
authors.initials: L
authors.lastname: Shi
authors.affiliation: Department of Physiology, China Medical University, Shenyang 110001, People's Republic of China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Bi
authors.affiliation: Department of Physiology, China Medical University, Shenyang 110001, People's Republic of China.
authors.forename: Wai
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of Physiology, China Medical University, Shenyang 110001, People's Republic of China.
authors.forename: Ling
authors.initials: L
authors.lastname: Qin
authors.affiliation: Department of Rheumatology and Immunology, First Affiliated Hospital, China Medical University, Shenyang 110001, People's Republic of China. Electronic address: yangpingtingting@163.com.
authors.forename: Pingting
authors.initials: P
authors.lastname: Yang
mesh_terms: D000818:Animals; D001596:Benzylamines; D001640:Bicuculline / Q000494:pharmacology; D054377:Chemokine CXCL12 / Q000494:pharmacology*; D003214:Conditioning, Classical / Q000187:drug effects*; D000080027:Cyclams; D005108:Extinction, Psychological / Q000187:drug effects*; D005239:Fear / Q000523:psychology*; D006571:Heterocyclic Compounds / Q000494:pharmacology; D008297:Male; D010721:Phosphinic Acids / Q000494:pharmacology; D011412:Propanolamines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D019718:Receptors, CXCR4 / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
chemical_list: D001596:Benzylamines; D054377:Chemokine CXCL12; C486264:Cxcr4 protein, rat; D000080027:Cyclams; D006571:Heterocyclic Compounds; D010721:Phosphinic Acids; D011412:Propanolamines; D019718:Receptors, CXCR4; C085075:CGP 55845A; D005680:gamma-Aminobutyric Acid; C088327:plerixafor; D001640:Bicuculline
keywords: Amygdala; CXCL12; CXCR4; Chemokines; Fear conditioning; GABA; Neuroinflammation; Neurotransmitter