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Low-temperature radical polymerization of achiral N-allyl-N-tert-butylacrylamide (AltBAAm) was conducted in toluene in the presence of chiral tartrates, such as diethyl L-tartrate (L-EtTar) and di-n-butyl L-tartrate. The 1H NMR spectra of the polymers obtained indicated progress of cyclopolymerization at low temperatures such as –80 °C. Optical properties of the poly(AltBAAm)s examined by optical rotation and circular dichroism measurements indicated asymmetric induction in the cyclopolymerization of achiral AltBAAm. For example, addition of L-EtTar at –80 °C provided the polymer with specific rotation of –4.8°. The tert-butyl groups of poly(AltBAAm)s were removed by treatment with CF3SO3H, transforming into poly(N-allylacrylamide)s [poly(AlAAm)s]. Then, stereochemistry in the stereorepeating unit was investigated by comparing 1H NMR signals of the poly(AlAAm)s with those of model compounds, cis- and trans-3-ethyl-4-methyl-2-pyrrolidones. Taking the negative specific rotation values of the poly(AltBAAm)s obtained with L-tartrates into account, it was revealed that (3S,4S)-trans-unit was predominantly formed through the hydrogen-bond-assisted complex formation of AltBAAm with L-tartrates.

Previous studies have demonstrated that rats subjected to single prolonged stress (SPS) exhibit posttraumatic stress disorder (PTSD)-like symptoms such as enhanced contextual fear in response to trauma related and trauma-unrelated events Furthermore we previously reported that upregulation of hippocampal glycine transporter 1 (GlyT-1) mRNA after context exposure could be the initial mechanism underlying impaired fear extinction in SPS rats To clarify the involvement of the hippocampal glycinergic system in impaired fear extinction in SPS rats we measured the time course of changes in the duration of freezing, and the hippocampal levels of Gly-T1 mRNA using contextual fear conditioning (FC) and extinction training We also used in vivo microdialysis to measure the concentration of extracellular glycine in the hippocampus during the time interval between FC and the first context exposure SPS rats exhibited increased and sustained contextual fear responses The enhanced contextual fear response in SPS rats was associated with a sustained increase in hippocampal levels of Gly-T1 mRNA after FC relative to sham rats and by a decrease in the extracellular glycine concentration GlyT-1 mRNA levels in rats that underwent repeated extinction training were significantly lower than in rats that did not undergo extinction training These findings indicate that reduced activity of the hippocampal glycinergic system could be closely involved in impaired fear extinction in SPS rats suggesting that activation of the glycinergic system by D-cycloserine or GlyT-1 inhibitors may ameliorate the impairment of fear extinction.

Previous studies have demonstrated that rats subjected to single prolonged stress (SPS) exhibit posttraumatic stress disorder (PTSD)-like symptoms such as enhanced contextual fear in response to trauma related and trauma-unrelated events Furthermore we previously reported that upregulation of hippocampal glycine transporter 1 (GlyT-1) mRNA after context exposure could be the initial mechanism underlying impaired fear extinction in SPS rats To clarify the involvement of the hippocampal glycinergic system in impaired fear extinction in SPS rats we measured the time course of changes in the duration of freezing, and the hippocampal levels of Gly-T1 mRNA using contextual fear conditioning (FC) and extinction training We also used in vivo microdialysis to measure the concentration of extracellular glycine in the hippocampus during the time interval between FC and the first context exposure SPS rats exhibited increased and sustained contextual fear responses The enhanced contextual fear response in SPS rats was associated with a sustained increase in hippocampal levels of Gly-T1 mRNA after FC relative to sham rats and by a decrease in the extracellular glycine concentration GlyT-1 mRNA levels in rats that underwent repeated extinction training were significantly lower than in rats that did not undergo extinction training These findings indicate that reduced activity of the hippocampal glycinergic system could be closely involved in impaired fear extinction in SPS rats suggesting that activation of the glycinergic system by D-cycloserine or GlyT-1 inhibitors may ameliorate the impairment of fear extinction.

Previous studies have demonstrated that rats subjected to single prolonged stress (SPS) exhibit posttraumatic stress disorder (PTSD)-like symptoms such as enhanced contextual fear in response to trauma related and trauma-unrelated events Furthermore we previously reported that upregulation of hippocampal glycine transporter 1 (GlyT-1) mRNA after context exposure could be the initial mechanism underlying impaired fear extinction in SPS rats To clarify the involvement of the hippocampal glycinergic system in impaired fear extinction in SPS rats we measured the time course of changes in the duration of freezing, and the hippocampal levels of Gly-T1 mRNA using contextual fear conditioning (FC) and extinction training We also used in vivo microdialysis to measure the concentration of extracellular glycine in the hippocampus during the time interval between FC and the first context exposure SPS rats exhibited increased and sustained contextual fear responses The enhanced contextual fear response in SPS rats was associated with a sustained increase in hippocampal levels of Gly-T1 mRNA after FC relative to sham rats and by a decrease in the extracellular glycine concentration GlyT-1 mRNA levels in rats that underwent repeated extinction training were significantly lower than in rats that did not undergo extinction training These findings indicate that reduced activity of the hippocampal glycinergic system could be closely involved in impaired fear extinction in SPS rats suggesting that activation of the glycinergic system by D-cycloserine or GlyT-1 inhibitors may ameliorate the impairment of fear extinction.