Acs Chem Neurosci
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Due to phylogenetic proximity to the human, zebrafish has been recognized as a reliable model to study Alzheimer's disease (AD) and other central nervous system disorders. Furthermore, metabotropic glutamate receptors have been previously reported to be impaired in brain from AD patients. Metabotropic glutamate 5 (mGlu5) receptors are G-protein coupled receptors proposed as potential targets for therapy of different neurodegenerative disorders. ⋯ This gender specific response was also observed in locomotor behavior, being significantly decreased only in male zebrafish. These results confirm the presence of mGlu5 receptors in brain from zebrafish and their gender specific modulation by selective antagonist treatment and suggest a role of these receptors on locomotor activity, which is affected in many disorders. In addition, our data point to zebrafish as a useful model to study mGlu receptor function in both healthy and pathological conditions.
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The mu opioid receptor gene undergoes extensive alternative splicing. Mu opioids can be divided into three classes based on the role of different groups of splice variants. Morphine and methadone require only full length seven transmembrane (7TM) variants for analgesia, whereas IBNtxA (3'-iodobenzyol-6β-naltrexamide) needs only truncated 6TM variants. ⋯ In exon 11 knockout mice, 125I-IDAPP binding was lowered to levels similar to 3H-DAMGO, which remained relatively unchanged compared to wild-type mice. 125I-IDAPP binding was totally lost in an exon 1/exon 11 knockout model lacking all Oprm1 variant expression, confirming that the drug was not cross labeling non-mu opioid receptors. These findings suggested that 125I-IDAPP labeled two populations of mu binding sites in wild-type mice, one corresponding to 7TM variants and the second dependent upon 6TM variants. Together, these data indicate that endomorphin analogs represent a unique, genetically defined, and distinct class of mu opioid analgesic.