dreadd agonist clozapine n oxide  (Tocris)

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