{"entity": "publication", "iuid": "0a80d47c46fa451bbe26e8895ae18c85", "timestamp": "2026-08-22T06:56:14.663Z", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/0a80d47c46fa451bbe26e8895ae18c85.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/0a80d47c46fa451bbe26e8895ae18c85"}}, "title": "Unexpected short- and long-term effects of chronic adolescent HU-210 exposure on emotional behavior.", "authors": [{"family": "Farinha-Ferreira", "given": "Miguel", "initials": "M"}, {"family": "Rei", "given": "N\u00e1dia", "initials": "N"}, {"family": "Fonseca-Gomes", "given": "Jo\u00e3o", "initials": "J"}, {"family": "Miranda-Louren\u00e7o", "given": "Catarina", "initials": "C"}, {"family": "Serr\u00e3o", "given": "Paula", "initials": "P"}, {"family": "Vaz", "given": "Sandra H", "initials": "SH"}, {"family": "Gomes", "given": "Joana I", "initials": "JI"}, {"family": "Martins", "given": "Val\u00e9ria", "initials": "V"}, {"family": "de Alves Pereira", "given": "Beatriz", "initials": "B"}, {"family": "Sebasti\u00e3o", "given": "Ana M", "initials": "AM"}], "type": "journal article", "published": "2022-08-15", "journal": {"title": "Neuropharmacology", "issn": "1873-7064", "volume": "214", "pages": "109155", "issn-l": null}, "abstract": "Chronic adolescent cannabinoid receptor agonist exposure has been shown to lead to persistent increases in depressive-like behaviors. This has been a key obstacle to the development of cannabinoid-based therapeutics. However, most of the published work has been performed with only three compounds, namely \u03949-tetrahydrocannabinol, CP55,940 and WIN55,212-2. Hypothesizing that different compounds may lead to distinct outcomes, we herein used the highly potent CB1R/CB2R full agonist HU-210, and first aimed at replicating cannabinoid-induced long-lasting effects, by exposing adolescent female Sprague-Dawley rats to increasing doses of HU-210, for 11 days and testing them at adulthood, after a 30-day drug washout. Surprisingly, HU-210 did not significantly impact adult anxious- or depressive-like behaviors. We then tested whether chronic adolescent HU-210 treatment resulted in short-term (24h) alterations in depressive-like behavior. Remarkably, HU-210 treatment simultaneously induced marked antidepressant- and prodepressant-like responses, in the modified forced swim (mFST) and sucrose preference tests (SPT), respectively. Hypothesizing that mFST results were a misleading artifact of HU-210-induced behavioral hyperreactivity to stress, we assessed plasmatic noradrenaline and corticosterone levels, under basal conditions and following an acute swim-stress episode. Notably, we found that while HU-210 did not alter basal noradrenaline or corticosterone levels, it greatly augmented the stress-induced increase in both. Our results show that, contrary to previously studied cannabinoid receptor agonists, HU-210 does not induce persisting depressive-like alterations, despite inducing marked short-term increases in stress-induced reactivity. By showing that not all cannabinoid receptor agonists may induce long-term negative effects, these results hold significant relevance for the development of cannabinoid-based therapeutics.", "doi": "10.1016/j.neuropharm.2022.109155", "pmid": "35660545", "labels": [], "xrefs": [{"db": "pii", "key": "S0028-3908(22)00214-3"}], "notes": [], "created": "2026-08-21T11:26:48.574Z", "modified": "2026-08-21T11:26:48.602Z"}