Abstract
The paraventricular nucleus of the thalamus (PVT) projects to the central nucleus of the amygdala and recent experimental evidence indicates a role for the PVT in conditioned fear. Furthermore, the PVT contains a high density of orexin receptors and fibers and acute injections of orexin antagonist into the PVT produce anxiolytic effects. The present study was done to determine if administration of a dual orexin receptor antagonist (DORA) in the region of the PVT interferes with the expression of conditioned fear in rats exposed to cued and contextual conditioning paradigms. Infusion of 0.5 μl of the DORA N-biphenyl-2-yl-1-[(1-methyl-1H-benzimidazol-2yl) sulfanyl] acetyl-L-prolinamide at a concentration of 0.1, 1.0, and 10 nmol had no effect on the freezing produced by exposing rats to an auditory cue or the context associated with foot shock. In contrast, the 1.0 and 10 nmol doses were anxiolytic in the social interaction test. The results of the present study do not support a role for orexin receptors in the PVT in the expression of learned fear. The finding that the 1.0 and 10 nmol doses of DORA in the PVT region were anxiolytic in the social interaction test is consistent with other studies indicating a role for orexins in the PVT in anxiety-like behaviors.
Highlights
Orexins, which consist of the bioactive orexin-A and orexin-B peptides, are synthesized exclusively in neurons in the hypothalamus
The present study investigated the role of orexin receptors in the paraventricular nucleus of the thalamus (PVT) in cued and contextual fear conditioning
The results show that microinjections of a dual orexin receptor antagonist (DORA) in the PVT did not attenuate the fear expressed following exposure of rats to cued and contextual fear conditioning paradigms
Summary
Orexins (hypocretins), which consist of the bioactive orexin-A and orexin-B peptides, are synthesized exclusively in neurons in the hypothalamus. These peptides act at G-protein coupled receptors called the orexin-1 (OX1R) and the orexin-2 receptors (OX2R). Other evidence shows that orexin neurons are activated in response to stressful conditions (Winsky-Sommerer et al, 2004) and that orexins contribute to anxiety-like behaviors. Systemic injections of the OX1R antagonist SB334867 blocked the behavioral and autonomic responses elicited in a rat model of panic (Johnson et al, 2010). Acute systemic injections of the dual orexin receptor antagonist (DORA) TCS-1102 reduced contextual fear as well as the defensive
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