Psilocybin shows efficacy to alleviate depression in human clinical trials for six or more months after only one or two treatments. Another hallucinogenic drug, esketamine, has recently been U.S. Food and Drug Administration (FDA)-approved as a rapid-acting antidepressant. The mechanistic basis for the antidepressant effects of psilocybin and ketamine appear to be conserved. The efficacy of these two medications has not, however, been directly compared either clinically or preclinically. Further, whether or not a profound subjective existential experience is necessary for psilocybin to have antidepressant effects is unknown. To address these questions, we tested psilocybin, lysergic acid diethylamide (LSD), and ketamine in a rat model for depression. As in humans, a single administration of psilocybin or LSD produced persistent antidepressant-like effects in our model. In contrast, ketamine produced only a transient antidepressant-like effect. Our results indicate that classic psychedelics may have therapeutic efficacy that is more persistent than that of ketamine, and also suggest that a subjective existential experience may not be necessary for therapeutic effects.

Experience with psychedelic drugs is associated with decreased risk of opioid abuse and dependence. Conversely, other illicit drug use history is largely associated with increased risk of opioid abuse and dependence. These findings suggest that psychedelics are associated with positive psychological characteristics and are consistent with prior reports suggesting efficacy in treatment of substance use disorders.

Persistent avoidance of stress-related stimuli following acute stress exposure predicts negative outcomes such as substance abuse and traumatic stress disorders. Previous work using a rat model showed that the central amygdala (CeA) plays an important role in avoidance of a predator odor stress-paired context. Here, we show that CeA projections to the lateral hypothalamus (LH) are preferentially activated in male rats that show avoidance of a predator odor-paired context (termed Avoider rats), that chemogenetic inhibition of CeA-LH projections attenuates avoidance in male Avoider rats, that chemogenetic stimulation of the CeA-LH circuit produces conditioned place avoidance (CPA) in otherwise naive male rats, and that avoidance behavior is associated with intrinsic properties of LH-projecting CeA cells. Collectively, these data show that CeA-LH projections are important for persistent avoidance of stress-related stimuli following acute stress exposure.

No abstract

<b><i>Introduction:</i></b> Immunoglobulin κC (IGKC)-positive tumor-infiltrating plasma cells are associated with better prognosis in node-negative breast cancer patients without adjuvant systemic therapy. In the present study we evaluated the prognostic significance of IGKC in breast cancer patients treated with adjuvant chemotherapy ± tamoxifen. <b><i>Methods:</i></b> IGKC expression was immunohistochemically analyzed in 193 breast cancer patients who were treated with adjuvant chemotherapy, either with cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) or 5-fluorouracil, epirubicin, and cyclophosphamide (FEC) between 1993 and 2001 with a median follow-up of 11 years. The prognostic impact of IGKC expression was evaluated by Kaplan-Meier survival analyses as well as uni- and multivariate Cox regression. An interaction term was used to investigate a possible association between tamoxifen treatment and prognostic effect of IGKC expression. <b><i>Results:</i></b> Kaplan-Meier analyses identified IGKC as a prognostic marker for metastasis-free survival (MFS): higher IGKC expression was associated with a better outcome (<i>p</i> = 0.02, log rank). Results of univariate Cox regression confirmed the prognostic impact of IGKC expression: patients with a strong IGKC expression had a longer MFS (hazard ratio [HR] 1.931; 95% confidence interval [CI] 1.087–3.431; <i>p</i> = 0.025). Multivariate Cox regression analysis showed the independent prognostic significance of IGKC expression (HR 2.070; 95% CI 1.088–3.938; <i>p</i> = 0.027). The interaction term confirmed a significant interaction between tamoxifen treatment and the prognostic impact of IGKC expression (<i>p</i>_interaction = 0.04). <b><i>Conclusion:</i></b> IGKC expression had an independent prognostic impact in early breast cancer patients who received adjuvant chemotherapy. There was a significant interaction with the use of tamoxifen.