Journal of neural transmission
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Successful adaptation to stress involves actions of glucocorticoid receptor (GR), a steroid-dependent transcription factor, abundant in hippocampus. Another transcription factor, nuclear factor kappa B (NFjB) is considered as an important stress sensor implicated in adaptive synaptic plasticity. Numerous stress-related genes are regulated by both hippocampal GR and NFjB, including neural cell adhesion molecules (NCAM and L1), involved in plasticity, and genes that encode apoptotic proteins (bax and bcl-2). ⋯ This resulted in its lower nuclear level relative to the nuclear NFjB. Such conditions did not affect proplastic induction of NCAM mRNA, but were related to the onset of proapoptotic signaling illustrated by relocation of mitochondrial Bcl-2 protein to its soluble cytoplasmic form. Because these Bcl-2 rearrangements were not reversed by subsequent acute stress, representing more stable alterations, it is concluded that chronic social isolation of Wistar rats led to the initiation of proapoptotic signaling that may be etiologically related to compromised adaptive response of central nervous system.
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N,N-dimethyltryptamine (DMT) is a potent plant hallucinogen that has also been found in human tissues. When ingested, DMT and related N,N-dialkyltryptamines produce an intense hallucinogenic state. Behavioral effects are mediated through various neurochemical mechanisms including activity at sigma-1 and serotonin receptors, modification of monoamine uptake and release, and competition for metabolic enzymes. ⋯ On the other hand, the tryptamines were very poor inhibitors of [(3)H]paroxetine binding to SERT and of [(3)H]dihydrotetrabenazine binding to VMAT2, resulting in high binding-to-uptake ratios. High binding-to-uptake ratios support the hypothesis that the tryptamines are transporter substrates, not uptake blockers, at both SERT and VMAT2, and also indicate that there are separate substrate and inhibitor binding sites within these transporters. The transporters may allow the accumulation of tryptamines within neurons to reach relatively high levels for sigma-1 receptor activation and to function as releasable transmitters.