{"entity": "journal", "iuid": "63b9867c835945dba834cdd73079567d", "timestamp": "2026-08-22T06:55:39.639Z", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/journal/Neuropharmacology.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/journal/Neuropharmacology"}}, "title": "Neuropharmacology", "issn": "1873-7064", "issn-l": null, "publications_count": 2, "publications": [{"entity": "publication", "iuid": "0a80d47c46fa451bbe26e8895ae18c85", "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"}, {"entity": "publication", "iuid": "47e538f412c744e1aacae0fdcfca7d28", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/47e538f412c744e1aacae0fdcfca7d28.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/47e538f412c744e1aacae0fdcfca7d28"}}, "title": "The high efficacy of muscarinic M4 receptor in D1 medium spiny neurons reverses striatal hyperdopaminergia.", "authors": [{"family": "Nair", "given": "Anu G", "initials": "AG"}, {"family": "Castro", "given": "Liliana R V", "initials": "LRV"}, {"family": "El Khoury", "given": "Marianne", "initials": "M"}, {"family": "Gorgievski", "given": "Victor", "initials": "V"}, {"family": "Giros", "given": "Bruno", "initials": "B"}, {"family": "Tzavara", "given": "Eleni T", "initials": "ET"}, {"family": "Hellgren-Kotaleski", "given": "Jeanette", "initials": "J"}, {"family": "Vincent", "given": "Pierre", "initials": "P"}], "type": "journal article", "published": "2019-03-01", "journal": {"title": "Neuropharmacology", "issn": "1873-7064", "volume": "146", "pages": "74-83", "issn-l": null}, "abstract": "The opposing action of dopamine and acetylcholine has long been known to play an important role in basal ganglia physiology. However, the quantitative analysis of dopamine and acetylcholine signal interaction has been difficult to perform in the native context because the striatum comprises mainly two subtypes of medium-sized spiny neurons (MSNs) on which these neuromodulators exert different actions. We used biosensor imaging in live brain slices of dorsomedial striatum to monitor changes in intracellular cAMP at the level of individual MSNs. We observed that the muscarinic agonist oxotremorine decreases cAMP selectively in the MSN subpopulation that also expresses D1 dopamine receptors, an action mediated by the M4 muscarinic receptor. This receptor has a high efficacy on cAMP signaling and can shut down the positive cAMP response induced by dopamine, at acetylcholine concentrations which are consistent with physiological levels. This supports our prediction based on theoretical modeling that acetylcholine could exert a tonic inhibition on striatal cAMP signaling, thus supporting the possibility that a pause in acetylcholine release is required for phasic dopamine to transduce a cAMP signal in D1 MSNs. In vivo experiments with acetylcholinesterase inhibitors donepezil and tacrine, as well as with the positive allosteric modulators of M4 receptor VU0152100 and VU0010010 show that this effect is sufficient to reverse the increased locomotor activity of DAT-knockout mice. This suggests that M4 receptors could be a novel therapeutic target to treat hyperactivity disorders.", "doi": "10.1016/j.neuropharm.2018.11.029", "pmid": "30468798", "labels": [], "xrefs": [{"db": "pii", "key": "S0028-3908(18)30861-X"}], "notes": [], "created": "2026-08-20T08:02:20.926Z", "modified": "2026-08-20T08:02:21.006Z"}], "created": "2026-08-20T08:02:20.963Z", "modified": "2026-08-20T08:02:20.963Z"}