dreadd agonist deschloroclozapine  (MedChemExpress)

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

Journal: bioRxiv

Article Title: Orbitofrontal noradrenaline mediates volatility-dependent adjustment of learning rate

doi: 10.64898/2025.12.11.693701

Figure Lengend Snippet: (A) Schematic representation of viral expression across subjects, showing the extent of AAV8-CaMKII-hM4D(Gi)-mCherry expression within the orbitofrontal cortex (OFC; VO and LO subregions). Each animal is represented as a separate layer (n = 12). (B) Representative fluorescence image illustrating AAV8-CaMKII-hM4D(Gi)-mCherry expression within the OFC (+4.2 mm from Bregma). (C) Mean number of reversals completed per 100 trials under vehicle (VEH) and deschloroclozapine (DCZ, 0.1 mg/kg, i.p.) treatments. (D) Post-reversal adaptation showing the trial-by-trial probability of selecting the high-probability lever following contingency reversals under VEH and DCZ conditions. (E) Proportions of high-reward probability lever-presses during the post-reversal period (left) and during stable phases (right) under VEH and DCZ treatments (***p < 0.001; n.s., not significant). (F) Average number of consecutive (perseverative) errors following reversals under VEH and DCZ conditions (***p < 0.001). (G) Probability of switching levers following different outcome types: rewarded (win), unrewarded (lose), high-probability (high), or low-probability (low) lever presses in the post-reversal phase (*p < 0.05). (H) Conditional probability of switching based on recent action–outcome sequences across the last two trials under VEH and DCZ treatments (*p < 0.05). (I) Learning rates (α) estimated from a standard reinforcement-learning model fitted to behavioral data under VEH and DCZ conditions (**p < 0.01). Data are presented as mean ± SEM.

Article Snippet: The DREADDs agonist deschloroclozapine (DCZ, MedChemExpress) was dissolved in dimethyl sulfoxide (DMSO) at a concentration of 50 mg/ml and stored at −80°C as a stock solution.

Techniques: Expressing, Fluorescence

Journal: bioRxiv

Article Title: Orbitofrontal noradrenaline mediates volatility-dependent adjustment of learning rate

doi: 10.64898/2025.12.11.693701

Figure Lengend Snippet: (A) Representative images showing the viral injection site in the orbitofrontal cortex (OFC; left) and retrogradely labeled mCherry-positive neurons in the locus coeruleus (LC; right). (B) Mean number of reversals per 100 trials under vehicle (VEH) and deschloroclozapine (DCZ; 0.1 mg/kg, i.p.) treatment, showing no effect of LC→OFC inhibition on the frequency of contingency reversals (n.s.). (C) Probability of switching levers following rewarded (win), unrewarded (lose), high-probability (high), or low-probability (low) lever presses in the post-reversal phase (p < 0.01). (D) Conditional switching probability following unrewarded outcomes, shown as a function of the total number of rewards obtained on the same lever across the preceding three trials (p < 0.01). Data are presented as mean ± SEM.

Article Snippet: The DREADDs agonist deschloroclozapine (DCZ, MedChemExpress) was dissolved in dimethyl sulfoxide (DMSO) at a concentration of 50 mg/ml and stored at −80°C as a stock solution.

Techniques: Injection, Labeling, Inhibition