dreadd agonist clozapine n oxide  (MedChemExpress)

Journal: Alzheimer's & Dementia

Article Title: Selective reduction of KCNA4 in vulnerable glutamatergic–serotonin neurons of the dorsal raphe nucleus in Alzheimer's disease

doi: 10.1002/alz.71317

Figure Lengend Snippet: The effects of chronic CM DRN modulation on htau behaviors. A, Graphical overview of the htau DREADDs experiment. Htau mice were intracranially administered hM3Dq ( n = 14), hM4Di ( n = 14), or control virus ( n = 9) at 2 months’ age. DREADDs agonist (CNO DHC) was administered via water bottle for 6 weeks. B, C, RNAscope assessment of Fos expression in virally transduced Tph2 + cells before CNO washout (acute) and after 7‐day washout. Two data points were collected per mouse in (C). No statistical test was performed in (C), data were qualitatively compared. D, E, NOR. D, Percent preference for novel object and (E), discrimination index. 1w ANOVA with Tukey post hoc. F, G, NSF. F, Latency to feed and (G), time spent in the corners of the arena during 10‐minute assessment period. H–K, EPM task. H, Percent of total time spent in open arm, (I) entries to open arm, (J) total distance traveled, and (K) average velocity during the task. L–R, Three‐chamber SIT. L, Total social interaction time, (M) number of social interactions, (N) social interaction time as a percentage of time spent in the social chamber, and (O) time spent in the center chamber. P–R, Representative heat maps, normalized within trial. D–F, H–K, 1w ANOVA with Dunnett post hoc. G, 1w Welch ANOVA with Dunnett post hoc. L–O, 1w ANOVA with Tukey post hoc. * p < 0.05, ** p < 0.01. 1w, one way; ANOVA, analysis of variance; CM, centromedial; CNO, clozapine‐n‐oxide; DHC, dihydrochloride; DREADDs, designer receptors exclusively activated by designer drugs; DRN, dorsal raphe nucleus; EPM, elevated plus maze; NOR, novel objection recognition; NSF, novelty‐induced suppression of feeding; SIT, social interaction test.

Article Snippet: After a 7‐day recovery period, mice were continuously administered the DREADD agonist CNO DHC (clozapine‐n‐oxide dihydrochloride; cat. #HB6149; Hello Bio) at a concentration of 6.06 mg/mL (equivalent to 5 mg/mL CNO) via water bottle in a home‐cage environment.

Techniques: Control, Virus, RNAscope, Expressing

Journal: iScience

Article Title: Dentate gyrus network regulation by somatostatin- and parvalbumin-expressing interneurons differentially impacts spatial memory processing

doi: 10.1016/j.isci.2026.115067

Figure Lengend Snippet: Effects of SST+ interneuron activation across different stages of spatial memory processing (A) Male and female SST-CRE mice ( n = 9 animals/group for encoding and consolidation; n = 14–15 animals/group for retrieval) are transduced to express Cre-dependent hM3Dq-mCitrine or EGFP (control) in DG. Beginning four weeks after viral transduction, SST+ interneurons were activated separately either during OLM encoding, consolidation, or retrieval, with two weeks of rest between OLM trials, which ended with a final trial in which vehicle is administered prior to encoding. (B) Timing of compound 21 (C21) administration relative to OLM encoding, consolidation, or retrieval. Mouse interaction with the moved vs. unmoved object is quantified to generate the OLM discrimination index (DI). (C–E) Discrimination index scores for encoding (C), consolidation (D), and retrieval (E) sessions in mice expressing EGFP or hM3Dq in SST+ interneurons. two-way ANOVA (Phase × AAV) revealed a significant main effect of AAV (F(1,58) = 7.40, p = 0.0086), indicating that the chemogenetic activation of SST+ interneurons influences DI performance independent of behavioral phase. Neither the main effect of Phase (F(2,58) = 1.69, p = 0.1936) nor the Phase × AAV interaction reached significance (F(2,58) = 2.41, p = 0.0985), though the interaction showed a trend. Closer inspection of the data showed the largest effects of SST+ interneuron activation on OLM encoding ( p = 0.0047, Tukey’s test) and retrieval ( p = 0.046, Tukey’s test), but had no effect on consolidation ( p = 0.8804). (F) Vehicle administration did not affect OLM encoding ( p = 0.755, n = 8–9 animals/group). For all panels, # p < 0.1, ∗ p < 0.05. Data are presented as mean ± SEM.

Article Snippet: DREADD agonist compound 21 , Tocris , 5548.

Techniques: Activation Assay, Control, Transduction, Expressing

Journal: Neurobiology of Stress

Article Title: Central medial and paraventricular thalamic afferents to the orbitofrontal cortex have differential effects on reversal learning

doi: 10.1016/j.ynstr.2026.100789

Figure Lengend Snippet: Inhibition of the CM-lOFC pathway disrupts reversal learning . A. Experimental timeline for Gi DREADD injections, cannulae implantation, and behavioral testing. B. Schematics showing cannulae placement in the lOFC (top) and minimum/maximum viral spread of the CM injections (bottom). C. Inhibiting the CM-lOFC pathway significantly increased trials to criterion during reversal learning compared to GFP controls (∗∗p = 0.0021, n = 10 per group, open symbols represent females) with no effect on discriminative learning (inset, p = 0.0996) D. CM-lOFC inhibition significantly increased perseverative errors (∗p = 0.0325); data represented as median ± 95% confidence interval.

Article Snippet: On day 3, a subset of animals went through the SD and CD stages of the reversal learning test, then received bilateral intracerebral injections into the OFC of the DREADD agonist clozapine-N-oxide (CNO, 300 μM, 0.75 μL per side, Tocris Bioscience, 4936) 25 min preceding the reversal learning task.

Techniques: Inhibition

Journal: Neurobiology of Stress

Article Title: Central medial and paraventricular thalamic afferents to the orbitofrontal cortex have differential effects on reversal learning

doi: 10.1016/j.ynstr.2026.100789

Figure Lengend Snippet: PVT-lOFC activation impedes reversal learning in non-stressed male rats . A. Experimental timeline for Gq DREADD injection into the PVT, cannulae implantation into the lOFC, and behavioral testing for males and females. B. Schematics showing cannulae placement in the lOFC (top) and min/max viral spread of the PVT injections (bottom). C. PVT-lOFC activation in non-stressed rats disrupted reversal learning in the aggregate data, open symbols represent females (∗∗∗p = 0.0002; n = 10-13 per group). In males (top inset; n = 5-7 per group), Gq DREADD activation significantly increased trials to criterion during reversal learning (∗∗∗∗p < 0.0001). In females (bottom inset; n = 5-6 per group), Gq DREADD activation had no effect on reversal learning (p = 0.2125). Gq activation had no effect on the SD and CD stages preceding the reversal learning test (right, p = 0.7157) D. PVT-lOFC activation significantly increased perseverative errors in the aggregate data as well as in males (top inset) and females (bottom inset) (aggregate: ∗∗∗∗p < 0.0001, males: ∗∗p = 0.0038, females: ∗p = 0.0152).

Article Snippet: On day 3, a subset of animals went through the SD and CD stages of the reversal learning test, then received bilateral intracerebral injections into the OFC of the DREADD agonist clozapine-N-oxide (CNO, 300 μM, 0.75 μL per side, Tocris Bioscience, 4936) 25 min preceding the reversal learning task.

Techniques: Activation Assay, Injection

Journal: Neurobiology of Stress

Article Title: Central medial and paraventricular thalamic afferents to the orbitofrontal cortex have differential effects on reversal learning

doi: 10.1016/j.ynstr.2026.100789

Figure Lengend Snippet: PVT-lOFC inhibition reverses the detrimental effects of chronic stress on reversal learning in male rats . A. Experimental timeline for Gi DREADD injection, CUS for males and females, and behavioral testing. B. Schematics showing cannulae placement in the lOFC (top) and min/max viral spread of the PVT injections (bottom). C. CUS increased trials to criterion compared to non-stressed controls, and this effect was not reversed by inhibition of the PVT-lOFC pathway in the aggregate data (left; ∗∗p = 0.0014; n = 11-12 per group). However, there was a sex difference. In males (top inset; n = 5-6 per group), CUS significantly increased trials to criterion, and PVT-lOFC inhibition reversed this effect (NS/GFP-CUS/GFP: ∗∗p = 0.0025, CUS/GFP-CUS/Gi: ∗∗p = 0.0040). In females (bottom inset; n = 6-7 per group), CUS significantly increased trials to criterion during reversal learning, but PVT-lOFC inhibition did not reverse this effect (NS/GFP-CUS/GFP: ∗p = 0.0403, CUS/GFP-CUS/Gi: p > 0.9999, NS/GFP-CUS/Gi: ∗p = 0.0487). There were no effects of any manipulation on the SD or CD phases (right, p = 0.1155). D. PVT-lOFC inactivation in stressed rats did not reverse the effects of stress on perseverative errors (left; ∗∗p = 0.0012). In males (top inset), CUS significantly increased perseverative errors (∗p = 0.0245), and PVT-lOFC inhibition in stressed rats decreased perseverative errors back to control levels, although the pairwise comparison was non-significant (p = 0.0623). In females (bottom inset), CUS significantly increased perseverative errors (∗p = 0.0430), and inhibiting PVT-lOFC in stressed rats did not reverse this effect (p > 0.9999).

Article Snippet: On day 3, a subset of animals went through the SD and CD stages of the reversal learning test, then received bilateral intracerebral injections into the OFC of the DREADD agonist clozapine-N-oxide (CNO, 300 μM, 0.75 μL per side, Tocris Bioscience, 4936) 25 min preceding the reversal learning task.

Techniques: Inhibition, Injection, Control, Comparison