Ability of predator odour exposure to elicit conditioned versus sensitised post traumatic stress disorder-like behaviours, and forebrain deltaFosB expression, in rats.

At present, exposure of a rodent to the odour of a predator is one of the most common animal models of post traumatic stress disorder (PTSD). Despite this, the model remains incompletely characterized, particularly in regard to within subject assessment of major PTSD-like behaviours. In an attempt to redress this situation, we have extensively characterized the two broad categories of behaviour that are considered to characterize PTSD, that is sensitized behaviours such as social withdrawal and hypervigilance and conditioned behaviours such as avoidance of trauma linked cues. Specifically, we determined the presence and duration of both conditioned and sensitized behaviours, in the same cohort of animals, after three exposures to predator odour. Conditioned fear was assessed on the basis of inhibition of locomotor activity upon return to context 2, 7, 14, 21, and 28 days after the last odour exposure session. To assess the impact on sensitization behaviours, we monitored acoustic startle responses and social interaction behaviour 4, 9, 16, 23, and 30 days after the last exposure session. In addition to examining the behavioural consequences associated with odour exposure, we also determined the key brain regions that were activated using DeltaFosB immunohistochemistry. Our results show that the two groups of behaviours thought to characterize PTSD (conditioned and sensitized) do not travel together in the predator odour model, with clear evidence of enduring changes in conditioned fear but little evidence of changes in social interaction or acoustic startle. With regard to associated patterns of activity in the brain, we observed that odour-exposed animals exhibited significantly higher numbers of FosB-positive nuclei in only the medial prefrontal cortex (mPFC), a finding that can be viewed as being consistent with the observed behavioural changes.

Functional asymmetry in the descending cardiovascular pathways from dorsomedial hypothalamic nucleus.

Neurons in the dorsomedial hypothalamus (DMH) play a key role in mediating tachycardia elicited by emotional stress. DMH activation by microinjections of the GABA(A) antagonist evokes tachycardia and physiological changes typically seen in experimental stress. DMH inhibition abolishes the tachycardia evoked by stress. Based on anatomic evidences for lateralization in the pathways from DMH, we investigated a possible inter-hemispheric difference in DMH-evoked cardiovascular responses. In anesthetized rats we compared changes in heart rate (HR), renal sympathetic activity (RSNA), mesenteric blood flow (MBF) and tail vascular conductance produced by activation of right (R) and left (L) sides of the DMH. We also evaluated the tachycardia produced by air jet stress after inhibition of R or L DMH. There were always greater increases in RSNA when bicuculline was injected ipsilaterally to the side where these parameters were recorded (average DeltaRSNA: L=+50% and R=+26%; P<0.05). Compared to pre-injection values, right DMH activation caused pronounced decrease (0.87+/-0.1% vs. 0.4+/-0.11%/mm Hg; P<0.05), whereas bicuculline methiodide (BMI) into left DMH produced no significant changes (0.95+/-0.09% vs. 1.04+/-0.25%/mm Hg) in tail vascular conductance. R or L DMH disinhibition produced decreases in MBF, but no differences in the range of these changes were observed. Activation of the right DMH caused greater tachycardia compared to the left DMH activation (average DeltaHR: R=+92 bpm; L=+48 bpm; P<0.05). Tachycardia evoked by air jet stress was smallest after right DMH inhibition (average DeltaHR: R=+57 bpm and L=+134 bpm; P<0.05). These results indicate that the descending cardiovascular pathways from DMH are predominantly lateralized and the right DMH might exert a prominent control on heart rate changes during emotional stress.

Blockade of 5-HT2A receptors suppresses hyperthermic but not cardiovascular responses to psychosocial stress in rats.

The aim of this study was to determine whether 5-HT2A receptors mediate cardiovascular and thermogenic responses to acute psychological stresses. For this purpose, adult male Wistar hooded rats instrumented for telemetric recordings of either electrocardiogram (ECG) (n=12) or arterial pressure (n=12) were subjected, on different days, to four 15-min episodes of social defeat. Prior to stress, animals received s.c. injection of the selective 5-HT2A receptor antagonist SR-46349B (trans-4-((3Z)3-[(2-dimethylaminoethyl)oxyimino]-3-(2-fluorophenyl)propen-1-yl)-phenol, hemifumarate) (at doses of 0.3, 1.0 and 3.0 mg/kg) or vehicle. The drug had no effect on basal heart rate or heart rate variability indexes, arterial pressure, and core body temperature. Social defeat elicited significant and substantial tachycardic (347+/-7 to 500+/-7 bpm), pressor (77+/-4 to 97+/-4 mm Hg) and hyperthermic (37.0+/-0.3 to 38.5+/-0.1 degrees C) responses. Blockade of 5-HT2A receptors, at all doses of the antagonist, completely prevented stress-induced hyperthermia. In contrast, stress-induced cardiovascular responses were not affected by the blockade (except small reduction of tachycardia by the highest dose of the drug). We conclude that in rats, 5-HT2A receptors mediate stress-induced hyperthermic responses, but are not involved in the genesis of stress-induced rises in heart rate or arterial pressure, and do not participate in cardiovascular control at rest.