Group-housed Sprague-Dawley (SD) rats exposed for 1 h to 2,5-dihydro-2,4,5-trimethylthiazoline (TMT, a component of fox feces) did not display changes in hippocampal serotonin (5-HT) metabolism and [3H]5-HT reuptake, compared to water or butyric acid. Such an observation extended to isolated SD and Fischer 344 rats. When group-housed SD rats were tested 1 week after a 1-h exposure to TMT, hippocampal 5-HT metabolism, [3H]5-HT reuptake, and [3H]paroxetine binding at the 5-HT transporter remained unchanged. This study questions TMT as a specific predatory stimulus as both butyric acid and TMT increased plasma corticosterone levels whilst leaving intact open field behaviour (at least in group-housed SD rats).
"At a systems level, SB may have some unusual effects and therefore is not entirely neutral. Although, unlike TMT, SB does not induce a large increase in plasma corticosterone in rats (Morrow et al., 2000), these effects are dependent on length of exposure and reexposure(Dias Soares et al., 2003). "
[Show abstract][Hide abstract] ABSTRACT: Amphetamine, which is known to cause sensitization, potentiates the hormonal and neurobiological signatures of stress and may also increase sensitivity to stress-inducing stimuli in limbic areas. Trimethylthiazoline (5μL TMT) is a chemical constituent of fox feces that evokes innate fear and activates the neuronal and hormonal signatures of stress in rats. We used blood oxygen level dependent (BOLD) MRI to test whether amphetamine sensitization (1mg/kg, i.p. ×3days) in female rats has a lasting effect on the neural response to a stress-evoking stimulus, the scent of a predator, during the postpartum period. The subiculum and dopamine-enriched midbrain VTA/SN of amphetamine-sensitized but not control mothers showed a greater BOLD signal response to predator odor than a control putrid scent. The greater responsiveness of these two brain regions following stimulant sensitization might impact neural processing in response to stressors in the maternal brain.
Brain research 12/2010; 1382:118-27. DOI:10.1016/j.brainres.2010.11.092 · 2.84 Impact Factor
"Using repeated swim to activate the HPA axis, the major finding of the present study is that inhibition of 5-HT clearance from ECF is one mechanism through which this occurs. However, we found that the decrease in 5-HT clearance rate following repeated swim was not a consequence of impaired function or expression of the high-affinity uptake mechanism for 5-HT, the SERT, a finding consistent with reports that other HPA-axis activators, including repeated restraint (Watanabe et al., 1993), fox odor exposure (Dias Sores et al., 2003), corticosterone ingestion (Fernandez et al., 2001), 3,4- methylenedioxymethamphetamine administration (Williams et al., 2005), and exercise (Chen et al., 2008), fail to alter SERT expression or [ 3 H]5-HT uptake in in vitro preparations from various brain regions, including hippocampus. "
[Show abstract][Hide abstract] ABSTRACT: Activation of the hypothalamic-pituitary-adrenal (HPA) axis is associated with increased extracellular serotonin (5-HT) in limbic brain regions. The mechanism through which this occurs remains unclear. One way could be via HPA axis-dependent impairment of serotonin transporter (SERT) function, the high-affinity uptake mechanism for 5-HT. Consistent with this idea, we found that 5-HT clearance rate in hippocampus was dramatically reduced in mice exposed to repeated swim, a stimulus known to activate the HPA axis. However, this phenomenon also occurred in mice lacking SERT, ruling out SERT as a mechanism. The organic cation transporter 3 (OCT3) is emerging as an important regulator of brain 5-HT. Moreover, corticosterone, which is released upon HPA axis activation, blocks 5-HT uptake by OCT3. Repeated swim produced a persistent elevation in plasma corticosterone, and, consistent with prolonged blockade by corticosterone, we found that OCT3 expression and function were reduced in these mice. Importantly, this effect of repeated swim to reduce 5-HT clearance rate was corticosterone dependent, as evidenced by its absence in adrenalectomized mice, in which plasma corticosterone levels were essentially undetectable. Behaviorally, mice subjected to repeated swim spent less time immobile in the tail suspension test than control mice, but responded similarly to SERT- and norepinephrine transporter-selective antidepressants. Together, these results show that reduced 5-HT clearance following HPA axis activation is likely mediated, at least in part, by the corticosterone-sensitive OCT3, and that drugs developed to selectively target OCT3 (unlike corticosterone) may be candidates for the development of novel antidepressant medications.
The Journal of Neuroscience : The Official Journal of the Society for Neuroscience 11/2010; 30(45):15185-95. DOI:10.1523/JNEUROSCI.2740-10.2010 · 6.34 Impact Factor
"Compared to restraint stress administered alone, TMT exposure plus restraint stress also moderately increases subsequent footshock avoidance (Brennan, Beck, & Servatius, 2006). However, McGregor et al. (2002) found that TMT does not increase anxiety-like behavior in rats exposed to the elevated plus maze or a general activity test 24 h later, and Dias Soares et al. (2003) found no TMT-induced sensitization effect in a subsequent open field test. Using CD-1 mice, Hebb et al. (2002, 2004) found that both TMT and butyric acid (an aversive but non-predator odor) sensitized responses to the light–dark test immediately after odor exposure, however there were no effects of either odor 24 h, 48 h, or 7 days later (Hebb et al., 2004). "
[Show abstract][Hide abstract] ABSTRACT: Prey animals such as rats display innate defensive responses when exposed to the odor of a predator, providing a valuable means of studying the neurobiology of anxiety. While the unconditioned behavioral and neural responses to a single predator odor exposure have been well documented, the paradigm can also be used to study learning-dependent adaptations that occur following repeated exposure to a stressor or associated stimuli. In developing preclinical models for human anxiety disorders this is advantageous, as anxiety disorders seldom involve a single acute experience of anxiety, but rather are chronic and/or recurring illnesses. Part 1 of this review summarizes current research on the three most commonly used predator-related odors: cat odor, ferret odor, and trimethylthiazoline (a component of fox odor). Part 2 reviews the learning-based behavioral and neural adaptations that underlie predator odor-induced context conditioning, one-trial tolerance, sensitization, habituation and dishabituation.
Neurobiology of Learning and Memory 09/2010; 94(4):435-45. DOI:10.1016/j.nlm.2010.09.009 · 3.65 Impact Factor
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