Ethopharmacological evaluation of antidepressant-like effect of serotonergic psychedelics in C57BL/6J male mice

1-(2,5-Dimethoxy-4-iodophenyl)-2-aminopropane (DOI): From an Obscure to Pivotal Member of the DOX Family of Serotonergic Psychedelic Agents – A Review

“…With respect to DOI, very low doses (0.1 mg/ kg) showed an antidepressant-like effect in animals (e.g., mouse forced-swim and tail-suspension tests) without inducing the HTR, and a role for 5-HT 2A receptors was implicated. 313 However, there has been some controversy regarding the use of serotonergic psychedelic agents for treatment-resistant depression and anxiety and whether or not this beneficial therapeutic effect is inextricably linked to their attendant hallucinogenic actions (for example, see: Jaster and Gonzaĺez-Maeso, 136 Takaba et al, 313 Lewis et al, 314 Cameron et al, 315 and Wallach et al 316 for extended discussions). Nearly 40 years ago, it was speculated that if such agents act via a 5-HT 2 agonist mechanism, "appropriate structural modifications could give rise to 5-HT 2 agonists that are not hallucinogenic.…”

“…Because serotonergic psychedelics are currently receiving renewed interest as potential psychotherapeutic agents it is, perhaps, logical that phenylalkylamines such as DOI be considered. With respect to DOI, very low doses (0.1 mg/kg) showed an antidepressant-like effect in animals (e.g., mouse forced-swim and tail-suspension tests) without inducing the HTR, and a role for 5-HT 2A receptors was implicated . However, there has been some controversy regarding the use of serotonergic psychedelic agents for treatment-resistant depression and anxiety and whether or not this beneficial therapeutic effect is inextricably linked to their attendant hallucinogenic actions (for example, see: Jaster and González-Maeso, Takaba et al, Lewis et al, Cameron et al, and Wallach et al for extended discussions).…”

Psilocybin-enhanced fear extinction linked to bidirectional modulation of cortical ensembles

“…After only a single dose, many patients report long-lasting improvements in depression and SUDs, as well as overall well-being for up to a year-a time-span implicating the involvement of cortically mediated long-term memory [3][4][5][6] . Therapeutic-like effects also have been observed in rodent models in many behavioral studies [7][8][9][10][11][12][13][14][15] , enabling the study of the neural mechanisms of psilocybin-enhanced mental health outcomes in mice.…”