Extract of Ginkgo biloba EGb761 facilitates extinction of conditioned fear measured by fear-potentiated startle.
A standard extract of Ginkgo biloba (EGb761) has been used in the treatment of various common geriatric complaints including vertigo, short-term memory loss, hearing loss, lack of attention, or vigilance. We demonstrated that acute systemic administration of EGb761 facilitated the acquisition of conditioned fear. Many studies suggest the neural mechanism underlies extinction is similar to the acquisition. This raises a possibility that EGb761 may modulate and accelerate the fear extinction process. We tested this possibility by using fear-potentiated startle (FPS) on laboratory rats. Acute systemic injection of EGb761 (10, 20, or 50 mg/kg) 30 min before extinction training facilitated extinction in a dose-dependent manner. Intra-amygdaloid infusion of EGb761 (28 ng/side, bilaterally) 10 min before extinction training also facilitated extinction. Control experiments showed that facilitation effect of EGb761 was not the result of impaired expression of conditioned fear or accelerated forgetting. Rats previously injected with EGb761 showed significant FPS after retraining. Extinction of conditioned fear appeared to result from acute drug effects rather than from toxic action. Systemic administration of EGb761 immediately after extinction training did not facilitate extinction, suggested the EGb761 facilitation effect is contributed to the acquisition phase of extinction learning. Western blot results showed that extinction induced amygdaloid extracellular signal-regulated kinase (ERK1/2) phosphorylation was significantly elevated by EGb761 treatment. Intra-amygdala injection of ERK1/2 inhibitor PD98059 completely blocked the EGb761 effect. Therefore, acute EGb761 administration modulated extinction of conditioned fear by activating ERK1/2.
Yang
Yi-Ling
YL
Department of Molecular Biology and Biochemistry, Institute of Biotechnology, National Chia-Yi University, Chia-Yi, Taiwan.
Su
Ya-Wen
YW
Ng
Ming-Chong
MC
Chao
Po-Kuan
PK
Tung
Li-Chu
LC
Lu
Kwok-Tung
KT
D000679:Amygdala / Q000187:drug effects / Q000201:enzymology; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects / Q000502:physiology; D003213:Conditioning, Psychological / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005108:Extinction, Psychological / Q000187:drug effects* / Q000502:physiology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000187:drug effects / Q000378:metabolism; D005239:Fear / Q000187:drug effects* / Q000502:physiology; D020441:Ginkgo biloba; D008297:Male; D008569:Memory Disorders / Q000188:drug therapy / Q000201:enzymology / Q000503:physiopathology; D018697:Nootropic Agents / Q000494:pharmacology / Q000627:therapeutic use; D010936:Plant Extracts / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D013216:Reflex, Startle / Q000187:drug effects* / Q000502:physiology; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology; D000096983:Ginkgo Extract
D004791:Enzyme Inhibitors; D048049:Extracellular Signal-Regulated MAP Kinases; D018697:Nootropic Agents; D010936:Plant Extracts; C063170:Ginkgo biloba extract; D000096983:Ginkgo Extract