{'fraction_non_alphanumeric': 0.022071307300509338, 'fraction_numerical': 0.003395585738539898, 'mean_word_length': 5.291814946619217, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
Antagonist-induced up-regulation of the putative epsilon opioid receptor in rat brain: comparison with kappa, mu and delta opioid receptors.

We reported previously that in the presence of appropriate blocking agents [3H]ethylketocyclazocine selectively labels a non-mu, non-delta, non-kappa binding site with opioid receptor characteristics. We now report that chronic treatment with the opiate antagonist naltrexone dramatically increases the number of these binding sites in rat brain, as well as the number of mu, delta and kappa receptors. This finding further supports the concept that the [3H]ethylketocyclazocine site is an opioid receptor and previously reported evidence indicating that it might be the beta-endorphin-specific epsilon receptor that has been hypothesized to exist for some time. The affinity of naltrexone for the putative epsilon site in vivo appears to be similar to its affinity for mu and delta receptors, since a single 30-mg naltrexone pellet was sufficient to induce a maximal rate of up-regulation for all three types of sites. In contrast, a maximal rate of kappa receptor up-regulation requires at least four naltrexone pellets and, therefore, the affinity of naltrexone for this site in vivo appears to be considerably lower than for the other sites. Unexpectedly, we found that the naltrexone-induced increase in binding to all four types of receptors continued to increase through 60 days of naltrexone exposure, the longest treatment period examined, and that the increases in receptor binding were linear with exposure time. This finding is contradictory to the generally held view that antagonist-induced opioid receptor up-regulation in brain increases asymptotically, leveling off after a relatively brief treatment period.