title: Minocycline attenuates interferon-α-induced impairments in rat fear extinction.
abstract: Extinction of conditioned fear is an important brain function for animals to adapt to a new environment. Accumulating evidence suggests that innate immune cytokines are involved in the pathology of psychotic disorders. However, the involvement of cytokines in fear dysregulation remains less investigated. In the present study, we investigated how interferon (IFN)-α disrupts the extinction of conditioned fear and propose an approach to rescue IFN-α-induced neurologic impairment.
  
  
  
  We used a rat model of auditory fear conditioning to study the effect of IFN-α on the fear memory process. IFN-α was infused directly into the amygdala of rats and examined the rats' behavioral response (freezing) to fear-conditioned stimuli. Immunohistochemical staining was used to examine the glia activity status of glia in the amygdala. The levels of the proinflammatory cytokines interleukin (IL)-1β and tumor necrosis factor (TNF)-α in the amygdala were measured by enzyme-linked immunosorbent assay. We also administrated minocycline, a microglial activation inhibitor, before the IFN-α infusion to testify the possibility to reverse the IFN-α-induced effects.
  
  
  
  Infusing the amygdala with IFN-α impaired the extinction of conditioned fear in rats and activated microglia and astrocytes in the amygdala. Administering minocycline prevented IFN-α from impairing fear extinction. The immunohistochemical and biochemical results show that minocycline inhibited IFN-α-induced microglial activation and reduced IL-1β and TNF-α production.
  
  
  
  Our findings suggest that IFN-α disrupts the extinction of auditory fear by activating glia in the amygdala and provides direction for clinical studies of novel treatments to modulate the innate immune system in patients with psychotic disorders.
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: Lijuan
authors.initials: L
authors.lastname: Shi
authors.affiliation: Department of Rheumatology and Immunology, First Affiliated Hospital, China Medical University, Shenyang, 110001, People's Republic of China.
authors.forename: Pingting
authors.initials: P
authors.lastname: Yang
authors.affiliation: Department of Rheumatology and Immunology, First Affiliated Hospital, China Medical University, Shenyang, 110001, People's Republic of China.
authors.forename: Jianing
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Physiology, China Medical University, Shenyang, 110001, People's Republic of China. qinlingling@yahoo.com.
authors.forename: Ling
authors.initials: L
authors.lastname: Qin
mesh_terms: D000161:Acoustic Stimulation; D000818:Animals; D003213:Conditioning, Psychological / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D005108:Extinction, Psychological / Q000187:drug effects* / Q000502:physiology; D005239:Fear / Q000187:drug effects* / Q000502:physiology / Q000523:psychology; D006801:Humans; D057967:Infusions, Intraventricular; D016898:Interferon-alpha / Q000008:administration & dosage* / Q000633:toxicity; D008297:Male; D008911:Minocycline / Q000008:administration & dosage*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D016898:Interferon-alpha; D008911:Minocycline
keywords: Amygdala; Astrocyte; Cytokine; Extinction; Fear conditioning; Microglia