Exogenous GRP or GRPR antagonist did not affect expression of conditioned fear.

<p><b>A</b>) 600 ng GRP or 3000 ng GRPR antagonist (D-Phe⁶,Leu-NHEt¹³,des-Met¹⁴)-Bombesin(6–14) was infused into the amygdala of C57BL/6 mice, that were conditioned with 6 CS-US pairings as in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0034963#pone-0034963-g002" target="_blank">Fig. 2C</a>, 10 min prior to testing freezing in the conditioning context 24 h later. <b>B</b>) Effect of intra-amygdala infusion of 600 ng GRP 10 min prior to testing freezing in response to the CS. <b>C</b>) Location of the bilateral injection sites determined from post-hoc histological analysis.</p

GRPR KO animals showed no differences in conditioned tast aversion (CTA) or neophobia.

<p><b>A</b>) CTA was evoked by pairing a novel taste, saccharin, with a LiCl injection to induce illness the day before testing (LiCl; n = 12 mice per group). Control animals were offered the novel taste saccharin but injected with NaCl (NaCl groups; n = 11 mice per group) or given only water to drink and injected with NaCl the previous day (saccharin naive groups; n = 12 mice per group). <b>B</b>) Attenuation of neophobia and neophobia were assessed by comparing the aversion to saccharin on first exposure (saccharin naive) with the aversion shown by mice that were exposed to saccharin the previous day (NaCl). On successive days the neophobia was attenuated by repeatedly being given the chance to drink saccharin flavored water.</p

Long-term potentiation in the LA is not changed in GRPR KO mice or by agonist/antagonist application.

<p><b>A</b>) Thalamic afferents were stimulated to evoke field excitatory postsynaptic potentials (fEPSPs) in the LA. Inset shows sample averaged traces (10 sweeps) from the 10 min baseline period (black) immediately before applying the tetanus (5×100 Hz/1 s trains, 20 s inter-train interval) and 40 min after the tetanus (grey). <b>B</b>) Mean ± s.e.m. of the change in fEPSP slope in the first 2 minutes after the tetanus (PTP) and 30–40 min after the tetanus. <b>C,D</b>) As in A,B except that cortical afferents were stimulated to evoke fEPSPs in the LA. <b>E,F</b>) Cortical afferents were stimulated at 30 s intervals to evoke EPSCs recorded from LA pyramidal neurons at −70 mV with the whole-cell voltage clamp technique. After a 10 min baseline 80 stimuli at 2 Hz were paired with depolarization to 30 mV. <b>G,H</b>) Long-term potentiation of cortico-LA fEPSPs induced by 5×100 Hz/1 s trains was not affected by bath application of 1 µM (D-Phe⁶,Leu-NHEt¹³,des-Met¹⁴)-Bombesin(6–14). Reducing inhibitory inputs by addition of 5 µM picrotoxin increased LTP. <b>I,J</b>) 1 µM GRP also did not significantly affect cortico-LA LTP.</p

Preparation, Antiepileptic Activity, and Cardiovascular Safety of Dihydropyrazoles as Brain-Penetrant T‑Type Calcium Channel Blockers

A series of dihydropyrazole derivatives was developed as potent, selective, and brain-penetrating T-type calcium channel blockers. An optimized derivative, compound <b>6c</b>, was advanced to in vivo studies, where it demonstrated efficacy in the WAG/Rij rat model of generalized nonconvulsive, absence-like epilepsy. Compound <b>6c</b> was not efficacious in the basolateral amygdala kindling rat model of temporal lobe epilepsy, and it led to prolongation of the PR interval in ECG recordings in rodents