Neuropeptide S-mediated control of fear expression and extinction: role of intercalated GABAergic neurons in the amygdala

Chronic Ethanol Potentiates the Effect of Neuropeptide S in the Basolateral Amygdala and Shows Increased Anxiolytic and Anti-Depressive Effects

“…We report an absence of NPS effects on evoked GABA IPSCs in saline-drinking mice. This observation correlates with a recent study showing that NPS perfusion positively modulates glutamatergic but not GABAergic synaptic transmission in the amygdala (Jungling et al, 2008). We go on to further show that after chronic EtOH, NPS application now does stimulate GABA IPSCs, suggesting that EtOH consumption has resulted in a gain of function, either via an increased expression of the NPSR or a greater effect of NPS on BLA neuronal excitability.…”

“…We began by examining whether the effects of NPS were altered in the BLA, a region of the brain known to modulate anxiety (for a review see, Koob (2000)). We began in this region because NPSR mRNA expression has been confirmed in the BLA (Jungling et al, 2008), and the NPSR has previously been shown to modulate activity in areas of the amygdala that converge on the BLA (Jungling et al, 2008;Meis et al, 2008;Dannlowski et al, 2011). Importantly, neuronal activity in the BLA has also been shown to influence directly the anxiety paradigms used in this study (Tye et al, 2011).…”

Persistent Increase of Alcohol-Seeking Evoked by Neuropeptide S: an Effect Mediated by the Hypothalamic Hypocretin System

“…Furthermore, the P rats show elevated anxiogenic-like behavior and it has been hypothesized that their excessive ethanol drinking is in part driven by ethanol's negatively reinforcing properties (ie, reduction of anxiety symptoms) (Stewart et al, 1993). NPS has anxiolytic-like effects in animal models of anxiety (Jungling et al, 2008;Xu et al, 2004); hence it is possible that this peptide decreases the incentive for ethanol intake in P rats by partially substituting for the anxiolytic-like effects of ethanol, thus reducing the motivation to consume the drug for its negatively reinforcing properties. Lastly, it cannot be excluded that genetic variants that directly affect the function of the NPS system have co-segregated and become fixed during the selection of the P line.…”

Learning not to Fear: Neural Correlates of Learned Safety

“…Fear extinction is an active relearning process in which animals are first trained in a fear conditioning protocol, and then with a series of unreinforced presentations of the CS alone (no longer paired with the aversive event) that leads to a reduction of conditioned fear response (Kaplan and Moore, 2011;Lattal and Maughan, 2012). New learning involved in fear extinction is in fact proposed to be a suppression of the expression of conditioned fear rather than the removal of the original fear memory (Bouton et al, 2006;Jungling et al, 2008;Maren and Quirk, 2004;Myers and Davis, 2007). Thus, both fear extinction and learned safety lead to the inhibition of responses evoked by fear, yet the approach and the involved behavioral repertoire may be distinct.…”