Infrared thermography was used to image changes in cutaneous temperature during a conditioned fear response to context. Changes in heart rate, arterial pressure, activity and body (i.p.) temperature were recorded at the same time by radio-telemetry, in addition to freezing immobility. A marked drop in tail and paws temperature (-5.3 and -7.5 degrees C, respectively, down to room temperature), which lasted for the entire duration of the response (30 min), was observed in fear-conditioned rats. In sham-conditioned rats, the drop was on average half the magnitude and duration. In contrast, temperature of the eye, head and back increased (between + 0.8 and + 1.5 degrees C), with no difference between the two groups of rats. There was a similar increase in body temperature although it was slightly higher and delayed in the fear-conditioned animals. Finally, ending of the fear response was associated with a gradual decrease in body temperature and a rebound increase in the temperature of the tail (+ 3.3 degrees C above baseline). This study shows that fear, and to some extent arousal, evokes a strong cutaneous vasoconstriction that is restricted to the tail and paws. This regionally specific reduction in blood flow may be part of a preparatory response to a possible fight and flight to reduce blood loss in the most exposed parts of the rat's body in case of injury. The data also show that the tail is the main part of the body used for dissipating internal heat accumulated during fear once the animal has returned to a safe environment.

Hypocretin/orexin has a well-established role in wakefulness and in the maintenance of arousal. Because stress is associated with arousal, it has been proposed that hypocretin is also involved in stress. However, it is not clear if this is true for all forms of stress. To clarify this issue, we compared four conditions combining high arousal with no or low stress (wakefulness and exploration) or high stress (contextual fear and restraint) in the rat. We looked at Fos expression in hypocretin neurons, hypocretin-1 levels in cerebrospinal fluid and cardiovascular and behavioural changes after pharmacological blockade with the dual hypocretin receptor antagonist, almorexant. Fos expression in hypocretin neurons was highest with wakefulness and exploration, also high with fear but not significant with restraint. Hypocretin-1 levels were consistent with this pattern, although the differences were not as marked. Hypocretin receptor blockade with almorexant reduced the pressor, tachycardic and locomotor responses of wakefulness and exploration as well as the pressor and sympathetic component of the tachycardic response of fear. In contrast, almorexant did not reduce the pressor and tachycardic responses of restraint and nor did it reduce the pressor, tachycardic and locomotor responses of another stressor, i.e. cold exposure. Thus, hypocretin is not involved in all forms of stress. Comparison of the different conditions suggests that, regardless of stress, hypocretin involvement occurs when the arousal associated with the response includes increased attention to environmental cues. When it does, hypocretin will at least contribute to the cardiovascular response. The findings are of clinical relevance to some forms of psychological stress.

The periaqueductal gray (PAG) has been traditionally considered to be an exit relay for defensive responses. Functional mapping of its subdivisions has advanced our knowledge of this structure, but synthesis remains difficult mainly because results from lesion and stimulation studies have not correlated perfectly. After using a strategy that combined both techniques and a reevaluation of the available literature on PAG function and connections, we propose here that freezing could be mediated by different PAG subdivisions depending on the presence of immediate danger or exposure to related signaling cues. These subdivisions are separate functional entities with distinct descending and ascending connections that are likely to play a role in different defensive responses. The existence of ascending connections also suggests that the PAG is not simply a final common path for defensive responses. For example, the possibility that indirect ascending connections to the cingulate cortex could play a role in the expression of freezing evoked by activation of the neural substrate of fear in the dorsal PAG has been considered.

Marks A, Vianna DM, Carrive P. Nonshivering thermogenesis without interscapular brown adipose tissue involvement during conditioned fear in the rat. Am J Physiol Regul Integr Comp Physiol 296: R1239 -R1247, 2009. First published February 11, 2009 doi:10.1152/ajpregu.90723.2008.-As with other forms of psychological stress, conditioned fear causes an increase in body temperature. The mechanisms underlying this stress-induced hyperthermia are not well understood, but previous research suggests that nonshivering thermogenesis might contribute, as it does during cold exposure. The major source of nonshivering thermogenesis in the rat is brown adipose tissue (BAT), and the largest BAT deposit in that species is in the interscapular area just below the skin. BAT is also under sympathetic control via ␤-adrenoceptors. If BAT contributes to fear-induced hyperthermia, then the interscapular skin should warm up faster than other skin areas, and this response should be suppressed by the ␤-adrenoceptor antagonist, propranolol. We tested this noninvasively by infrared thermography. In conscious rats, 30 min of contextual fear caused hyperthermia (as indicated by a ϩ1.5°C increase in lumbar back skin temperature) and increased the difference in temperature between interscapular and lumbar back skin (TiScap Ϫ TBack) by ϩ1°C. Propranolol (10 mg/kg ip) completely abolished this hyperthermia; however, the TiScap-TBack increase was not reduced. In contrast, exposure to cold air (4°C) induced a ϩ2.7°C increase in TiScap-TBack, which was reduced to ϩ1°C after propranolol. The results show that conditioned fear-induced hyperthermia is of nonshivering origin and mediated by ␤-adrenoceptors, but interscapular BAT does not contribute to it and does not appear to be activated, either. stress hyperthermia; thermoregulation; tail skin; freezing; sympathetic responses MANY PSYCHOLOGICAL STRESSORS can cause an increase in body temperature (2,11,25,29), an effect also known as stress hyperthermia (2, 18). There are two ways in which body temperature can be elevated, either by reducing heat loss or by increasing heat production. The most effective way of reducing heat loss in the animal is through skin vasoconstriction (13). Increased heat production or thermogenesis can be achieved via two mechanisms: shivering thermogenesis if the heat comes from contracting skeletal muscles (15) or nonshivering thermogenesis if it comes from elsewhere (13, 17). The best studied effector of nonshivering thermogenesis is brown adipose tissue (BAT), which is under sympathetic control (4, 20). Only present in mammals, BAT is classically called into action during cold exposure. It is most often found in newborns, small mammals, and hibernating species, which are the ones who are most prone to suffer from cold stress, but it might also be functional in adult humans (6,20). Moreover, it is the only site where cold adaptation, that is, the development of increased recruitable thermogenic capacity in response to chronic cold exposure, occurs (4, 9, 12). In rats and ...