Neuropeptide S in the basolateral amygdala mediates an adaptive behavioral stress response in a rat model of posttraumatic stress disorder by increasing the expression of BDNF and the neuropeptide YY1 receptor.

Neuropeptide S (NPS) is a regulatory peptide that has anxiolytic and arousal-promoting effects in rodents. We used an animal model of posttraumatic stress disorder (PTSD) to assess long-term behavioral effects of a single dose of NPS, microinjected into the basolateral amygdala (BLA) 1h following exposure to predator-scent stress (PSS). To elucidate the molecular mechanism by which NPS attenuates behavioral stress responses, expression levels of neuropeptide Y (NPY), NPY-Y1 receptor (NPY-Y1R), and brain-derived neurotrophic factor (BDNF) were evaluated in the hippocampus. The behavioral and molecular effects of NPS receptor antagonist (NPS-RA), NPY-Y1R antagonist (NPY-Y1RA), or both administered centrally were evaluated in the same manner. Circulating corticosterone levels were measured at different time points following PSS-exposure. Immediate post-exposure treatment with NPS had a marked protective effect; BLA microinfusion of NPS completely abolished the extreme behavioral response to PSS, restored the decreased expression of BDNF and, unexpectedly, PY-Y1R, but didn't affect the decreased expression of NPY. BLA microinfusion of both NPY-Y1RA and NPS-RA together had an additive effect, which completely prevented the anxiolytic effects of NPS in rats exposed to PSS and disrupted the expression of NPY-Y1R in the hippocampus following NPS infusion. It may therefore be hypothesized that NPS acts, directly or indirectly, on both the NPY-Y1R and NPS receptors and that the cross-talk between NPS and NPY-Y1R may be necessary for the anxiolytic effects of NPS post-exposure. The NPS system might thus contribute to a potential endogenous mechanism underlying the shift towards adaptive behavioral response and thereby might be relevant as a pharmacological target for attenuating stress-related sequelae.

[Between neurology and psychiatry].

In this review we will discuss the broad spectrum of possible relationships between the fields of neurology and psychiatry alongside weighing the pros and cons of each alternative relationship. This is in the hope that such discussions will allow an informed decision regarding the construction of future relations between these two areas. The possible connections between the areas are discussed in light of possible relationships that exist between the two groups in the mathematical world with reference to the proposed solutions to the psychophysical mind-body problem.

Setting apart the affected: the use of behavioral criteria in animal models of post traumatic stress disorder.

Post-traumatic stress disorder (PTSD) affects about 20-30% of exposed individuals. Clinical studies of PTSD generally employ stringent criteria for inclusion in study populations, and yet in animal studies the data collection and analysis are generally expressed as a function of exposed vs nonexposed populations, regardless of individual variation in response. Prior data support an approach to animal models analogous to inclusion criteria in clinical studies. This series of studies sought to assess prevalence rates of maladaptive vs adaptive responses determined according to a more stringent approach to the concept of inclusion/exclusion criteria (cutoff behavioral criteria-CBC), consisting of two successive behavioral tests (elevated plus maze and acoustic startle response tests). The rats were exposed to stressors in two different paradigms; exposure to a predator and underwater trauma. The prevalence rates of maladaptive responses to stress in these two distinct models dropped over time from 90% in the acute phase to 25% enduring/maladaptive response at 7 days, to remain constant over 30 days. As setting the affected individuals apart from the unaffected approximates clinical studies, it might also help to clarify some of the pending issues in PTSD research.

Effect of intraperitoneal mRNA antisense-oligodeoxynucleotides to cholecystokinin on anxiety-like and learning behaviors in rats: association with pre-experimental stress.

RATIONALE: Cholecystokinin and its analogs generate anxiety in humans and measurable anxiety-like behaviors in rats. Cholecystokinin receptor blockers have been reported to have variable effects in the treatment of anxiety disorders. We demonstrated that intracerebroventricular administration of Cholecystokinin-antisense oligodeoxynucleotides (ASODN) for 3 days significantly diminished anxiety-like behavior in rats. OBJECTIVE: This study was designed to examine the effects of peripheral (intraperitoneal) administration of Cholecystokinin-ASODN on anxiety-like and learning behaviors in rats, in general and in a pre-experiment stress paradigm. METHODS: In the first study Cholecystokinin-ASODN was injected intraperitoneally to rats five times at 24-h intervals. Control groups received injections of either a scrambled oligodeoxynucleotide (ScrODN) or vehicle. On the sixth day, the rats were assessed in the elevated plus-maze paradigm and in the Morris water maze. In the second study, rats were pre-exposed to a cat for 10 min as a model for psychological stress, and then treated with intraperitoneal Cholecystokinin-ASODN and tested in both paradigms. RESULTS: The results show that for intact rats, intraperitoneal Cholecystokinin-ASODN significantly increased anxiety-like behavior and impaired retention performance in the Morris water maze, compared to both control groups. In stressed rats, Cholecystokinin-ASODN reduced anxiety-like behaviors in the plus-maze and improved performance in the water maze compared with controls. CONCLUSIONS: These results indicate that the anxiolytic effect of intraperitoneal Cholecystokinin-ASODN may be dependent on the baseline endogenous level of stress (i.e., on the Cholecystokinin levels). Basal endogenous levels of Cholecystokinin, as well as exogenous dosage of Cholecystokinin agonists and/or anxiolytic agents, appear to play an important role in the expression and/or control of anxiety-related behaviors in rats.