Intra-amygdaloid infusion of Ginkgo biloba leaf extract (EGb761) facilitates fear-potentiated startle in rats.

RATIONALE: Ginkgo biloba extract, EGb761, is one of the most commonly used herbal supplements throughout Western society. It has been used in the treatment of various common geriatric complaints including short-term memory loss. We showed that acute systemic administration of EGb761 enhanced fear-potentiated startle (FPS) in rats. Little is known about the behavioral effects of centrally administered EGb761 on FPS. OBJECTIVE: The current study was performed to evaluate the involvement of basolateral nucleus of amygdala (BLA) in the EGb761 facilitation effect on FPS. METHODS AND RESULT: Male adult SD rats were used. EGb761 was infused into cerebroventricle or basolateral nucleus of amygdala 10 min prior to fear conditioning. Animals were then tested for FPS 24 h later. Results showed that (1) intra-cerebroventricular infusion of EGb761 (0.1, 1.0, or 3.0 microg/3.0 microl per side, bilaterally) and intra-amygdaloid infusion of EGb761 (1.0, 14.0, or 28.0 ng/microl per side, bilaterally) 30 and 10 min prior to fear conditioning, respectively, facilitated FPS in a dose-dependent manner. (2) Administration of EGb761 did not impair an animal's basal startle response or pain perception. (3) Subsequent control experiment's results indicated that the facilitation effect of EGb761 on the acquisition was not due to anxiogenic effect or non-specific effect. CONCLUSIONS: These results suggested that a single dose of EGb761 also has memory-enhancing effects in young animals. In addition, BLA is the central locus for EGb761 facilitation effect on FPS.

Glutamate NMDA receptors within the amygdala participate in the modulatory effect of glucocorticoids on extinction of conditioned fear in rats.

Recent results show that brain glucocorticoids are involved in the dysregulation of fear memory extinction in post-traumatic stress disorder patients. The present study was aimed to elucidate the possible mechanism of glucocorticoids on the conditioned fear extinction. To achieve these goals, male SD rats, fear-potentiated startle paradigm, and Western blot were used. We found that (1) systemic administration of the synthetic glucocorticoid agonist dexamethasone (DEX) facilitated extinction of conditioned fear in a dose-dependent manner (0.05, 0.1, 0.5, or 1.0 mg/kg, i.p.); (2) systemic administration of the glutamate NMDA receptor antagonist (+/-)-HA966 (6.0 mg/kg, i.p.) and intra-amygdala infusion of the NMDA receptor antagonists MK801 (0.5 ng/side, bilaterally) or D,L-2-amino-5-phosphonovaleric acid (AP5, 2.0 ng/side, bilaterally) blocked the DEX facilitation effect; (3) the corticosteroid synthesis inhibitor metyrapone (25 mg/kg. s.c.) blocked extinction and this was prevented by co-administration of NMDA receptor agonist D-cycloserine (DCS, 5.0 mg/kg, i.p.); (4) co-administration of DEX and DCS in subthreshold doses provided a synergistic facilitation effect on extinction (0.2 and 5 mg/kg, respectively). Control experiments indicated that co-administration of DEX and DCS did not alter the expression of conditioned fear and the effect was not due to lasting damage to the amygdala. These results suggest that glutamate NMDA receptors within the amygdala participate in the modulatory effect of glucocorticoids on extinction.

Extracellular signal-regulated kinase-mediated IL-1-induced cortical neuron damage during traumatic brain injury.

Traumatic brain injury (TBI) is one of the most prevalent causes of morbidity and mortality in youth. Interleukin-1 (IL-1) has many roles in the brain in addition to mediating glial inflammatory response; it has also been implicated in neurodegenerative diseases. We demonstrated the signal transduction pathway of IL-1 overproduction-induced cortical neuron loss during TBI. A calibrated weight-drop device (450 g weight and 2m height) was used to induce TBI in adult male Sprague-Dawley rats under general anesthesia (sodium pentobarbital: 40 mg/kg, i.p.). Expression of interleukin-1alpha (IL-1alpha), interleukin-1beta (IL-1beta), extracellular signal-regulated kinase (ERK), Jun, and p-38 were determined by Western blotting and RT-PCR. Neuronal damage was evaluated by microscopic examination. We found both mRNA and proteins of cortical IL-1alpha and IL-1beta increased three hours after TBI. Phosphorylation of ERK significantly increased but there were no significant effects on cortical expression of ERK, Jun and p-38. Administration of ERK inhibitor, PD98059, IL-1alpha antibody and IL-1beta antibody protected animals from TBI-induced neuronal damage. Our results suggest that TBI-induced cortical neuron death was mediated by the IL-1 receptor through ERK phosphorylation.