Gastrin-releasing peptide attenuates fear memory reconsolidation.

BACKGROUND: Gastrin Releasing Peptide (GRP) may play a role in fear learning. The GRP Receptor is expressed in the basolateral amygdala and hippocampus, and central administration of GRP mediates fear learning. The effects of GRP on reconsolidation, however, have been minimally explored. Reconsolidation, the process by which formed memories are rendered labile following recall, provides a window of opportunity for pharmacological intervention. Although evidence suggests the window of opportunity to alter reactivated consolidation memory can be as long as 6 h, shorter intervals have not been extensively investigated. METHOD: Male Sprague-Dawley rats received six 1.0 mA continuous footshocks. 24 h later, were re-exposed to the context (shock chamber). Immediately following memory retrieval rats received i.p. injection of GRP (10 nmol/kg), Flumazenil (1 mg/kg), GRP + Flumazenil (10 nmol/kg GRP with 1 mg/kg Flumazenil), or Vehicle. Other groups received GRP or Vehicle at 0, 10, 30, or 60 min post-reactivation. 24 h and 5 days later rats were assessed for fear expression upon re-exposure to the fearful stimulus. RESULTS: GRP significantly attenuated the reconsolidation of learned fear when administered immediately (but not 10 min or longer) following recall. Some of the variability in the impact of treatments aimed at disrupting fear memories may be governed, in part, by the time-frame of the reconsolidation window. Our results indicate that the effect of immediate administration persisted for at least 5 days. Co-administration of benzodiazepine-receptor antagonist Flumazenil blocked this effect, suggesting the effect is mediated via a GABAergic mechanism.

Ability of palatable food consumption to buffer against the short- and long-term behavioral consequences of social defeat exposure during juvenility in rats.

In adult rats, access to a palatable diet can buffer against the effects of stressors. Approximately 10% of all adolescents are repeatedly victimized by their peers raising the possibility that palatable food consumption may be relevant to this developmental window. This study assessed the long-term impact of juvenile social defeat exposure on anxiety and depressive-like behavior and whether daily limited access to a palatable diet moderated these behavioral consequences. We also investigated the impact of the palatable diet on behavior during the defeat sessions. Juvenile rats were exposed to either a different adult resident rat (Stress) or handling (Control) from postnatal day (PD) 28-34. All rats had ad libitum access to either chow alone or both chow and limited access (4h/day) to palatable food commencing on PD 21. Results showed that during the defeat sessions, juvenile rats with access to the palatable diet spent less time in submissive postures and displayed significantly longer latencies to submit to the resident. In adulthood, previous exposure to juvenile social defeat resulted in a mild anxiogenic profile in the open field among rats with access to Chow only. Furthermore, defeated rats, regardless of diet, displayed reduced locomotor activity and increased social interaction as adults. These findings suggested only minimal enduring negative consequences from juvenile social defeat exposure which made it challenging to assess potential stress-buffering effects of the palatable diet. This was not the case during the defeat sessions where previous exposure to palatable food appeared protective against the acute stressor effects.

Anxiolytic activity and active principles of Piper amalago (Piperaceae), a medicinal plant used by the Q'eqchi' Maya to treat susto, a culture-bound illness.

ETHNOPHARMACOLOGICAL RELEVANCE: The medicinal plant, Piper amalago L. (Piperaceae), is used traditionally by Q'eqchi' Maya healers for the treatment of "susto" a culture-bound syndrome. Previous research suggests that susto symptoms may be a manifestation of anxiety. The objectives were to characterize the effect of ethanolic extract of P. amalago in behavioral assays of anxiety at doses representative of traditional use and to isolate active principles. MATERIALS AND METHODS: Rats treated orally with low dose ethanolic extracts of P. amalago leaves (8-75mg/kg) were tested in several behavioral paradigms including the elevated plus maze (EPM), social interaction (SI), and conditioned emotional response (CER) tests, and compared to diazepam, a positive control. The active anxiolytic principle was isolated by bioassay guided isolation using an in vitro GABAA competitive binding assay. RESULTS: Extracts had significant anxiolytic activity in all behavioral tests, with the strongest activity in the SI and the CER paradigms. In an in vitro GABAA competitive binding assay, a 66.5µg/mL concentration of P. amalago ethanol extract displaced 50% of the GABAA-BZD receptor ligand [(3)H]-Flunitrazepam. Bioassay-guided fractionation identified a furofuran lignan, a molecule with structural similarity to yangambin, with high affinity for the GABAA-BZD receptor as the principle bioactive. CONCLUSION: The results suggest that the ethnobotanical use of this plant may have a pharmacological basis in its anxiolytic activity, as demonstrated in animal behaviour tests.

Effects of electroconvulsive seizures on depression-related behavior, memory and neurochemical changes in Wistar and Wistar-Kyoto rats.

BACKGROUND: Investigations in healthy outbred rat strains have shown a potential role for brain-derived neurotrophic factor (BDNF) and the hypothalamic-pituitary-adrenal (HPA) axis in the antidepressant and memory side effects of electroconvulsive therapy (ECT, or ECS in animals). The Wistar-Kyoto (WKY) rat strain is used as a genetic model of depression yet no studies to date have directly compared the impact of ECS on the WKY strain to its healthy outbred control (Wistar). OBJECTIVE: The objective of this study is to examine behavioral (antidepressant and retrograde memory) and neurochemical (BDNF and HPA axis) changes immediately (1day) and at a longer delay (7days) after repeated ECS (5 daily administrations) in WKY and Wistar rats. METHODS: Male Wistar and WKY rats received 5days of repeated ECS or sham treatment and were assessed 1 and 7days later for 1) depression-like behavior and mobility; 2) retrograde memory; and 3) brain BDNF protein, brain corticotropin-releasing factor (CRF) and plasma corticosterone levels. RESULTS: Both strains showed the expected antidepressant response and retrograde memory impairments at 1day following ECS, which were sustained at 7days. In addition, at 1day after ECS, Wistar and WKY rats showed similar elevations in brain BDNF and extra-hypothalamic CRF and no change in plasma corticosterone. At 7days after ECS, Wistar rats showed sustained elevations of brain BDNF and CRF, whereas WKY rats showed a normalization of brain BDNF, despite sustained elevations of brain CRF. CONCLUSIONS: The model of 5 daily ECS was effective at eliciting behavioral and neurochemical changes in both strains. A temporal association was observed between brain CRF levels, but not BDNF, and measures of antidepressant effectiveness of ECS and retrograde memory impairments suggesting that extra-hypothalamic CRF may be a potential important contributor to these behavioral effects after repeated ECS/ECT.

Nesfatin-1 increases anxiety- and fear-related behaviors in the rat.

RATIONALE: Nesfatin-1, derived from the protein NEFA/nucleobindin2 (NUCB2), is a newly identified peptide that acts as a potent satiety agent. It has been reported that peptides involved in the regulation of ingestive behavior are also involved in the regulation of the stress response. However, the relation between nesfatin-1 and stressor-related behaviors like anxiety and/or fear has not yet been investigated. OBJECTIVE: The effects of intracerebroventricular (ICV) injection of nesfatin-1 (0, 5, and 25 pmol/3 microl) were assessed in several paradigms that are thought to reflect anxiety and/or fear in rats. RESULTS: Consistent with an anxiogenic effect, nesfatin-1 dose-dependently decreased the percentage of time spent on the open arms of the elevated plus maze, increased latency to approach, and decreased consumption of a palatable snack in an anxiogenic (unfamiliar) environment. Moreover, ICV nesfatin-1 increased the fear-potentiated startle response and the time spent freezing to both context and conditioned cues in a conditioned emotional response test. CONCLUSIONS: These findings suggest that in addition to its role as a satiety peptide, nesfatin-1 may also be involved in the mediation of anxiety- and/or fear-related responses.