Local prefrontal CX516 improved object-in-place recognition in male Lister hooded rats at 0.3 μg/μl, but not 0.1 μg/μl, without significantly changing total exploration. In a separate study of stressed Wistar–Kyoto rats, local CX-516 improved novel-object recognition and partially restored sucrose intake; the higher dose also increased exploration. These task- and condition-specific effects do not establish a general cognitive benefit. [2,3]
In male Tm4sf2−/y mice, CX516 at 5 mg/kg intraperitoneally twice daily for five days restored hippocampal AMPAR rectification and long-term potentiation toward wild-type vehicle values. These endpoints were measured in slices after systemic treatment; reported n values for the physiological results denote cells or slices. [4]
Local prefrontal CX516 and associative recognition memory
Animal study · Male Lister hooded rats, 300–350 g at experiment start; object-in-place task; final CX516 analysis n = 8. [2]
Bilateral mPFC CX516 improved object-in-place discrimination at 0.3 μg/μl, whereas 0.1 μg/μl did not significantly differ from saline. Total exploration was unchanged. Separate CX546 and MMPIP treatments were ineffective; no combination benefit was tested.
Conditions shared by the study groups
- Route
- Bilateral intra-mPFC
- Frequency
- Within-subject dose sessions; at least 3 days between infusions
- Treatment course
- Administered after sample, during 5 min delay
- Vehicle
- 0.9% saline
- CX516 concentration series
- Model: Male Lister hooded rats; final n = 8
Methods and source locations
Compound reported in the paper: CX516; Compound label in the paper: CX516
Historical AdooQ sourcing can be stated for this paper only; it does not validate any current A12349 lot.
Experiment 3 results; Figure 6A–B and caption; Table 2; Materials and Methods: Subjects, Drug infusions, Behavioral testing, Statistical analysis
Object-in-place discrimination ratio: Within-subject fully counterbalanced Latin square; blinded experimenter; doses compared with their own vehicle control. No exact bar heights extracted. — Experiment 3 results; Figure 6A and caption
Total object exploration in sample and test phases: No significant CX516 effect on total exploration. Table 2 displays mean ± SEM; sample duration 5 min, test duration 3 min. — Experiment 3 results; Table 2 and footnote
CX516 concentration series · Experiment 3 results; Figure 6A–B and caption; Table 2; Materials and Methods: Subjects, Drug infusions, Behavioral testing, Statistical analysis
Prefrontal CX-516 in stressed Wistar–Kyoto rats
Animal study · Male Wistar–Kyoto rats exposed to chronic mild stress and non-stressed controls; Experiment 4, n = 8 per stress-by-dose group. [3]
Local CX-516 restored novel-object recognition in stressed animals and partially restored sucrose intake. The higher dose also increased exploratory behavior in both stress conditions, limiting a purely memory-specific interpretation. Locomotor activity was not significantly altered.
Conditions shared by the study groups
- Route
- Unilateral left intra-mPFC
- Frequency
- Two administrations separated by four days
- Treatment course
- After NOR exposure; four days later before final sucrose test
- Vehicle
- 0.9% sterile saline
- CX-516 dose series in stressed and non-stressed rats
- Model: Male WKY; n = 8 per stress-by-dose group
Methods and source locations
Compound reported in the paper: CX516; Compound label in the paper: CX-516
Supports model- and task-specific behavioral effects; no clinical antidepressant efficacy or current-lot validation.
Methods: Study design, Experiment 4, NOR test, Intracranial injections, Drugs, Statistical analysis; Results: Antidepressant-like effects of the ampakine CX-516; Figure 6A–D and caption; Discussion limits
Novel-object recognition, exploration and locomotor activity: NOR retention trial one hour after exposure; blinded observer. Recognition index = (novel − familiar exploration)/total exploration. Values plotted as means + SEM; no exact means read from bars. — Experiment 4 results; Figure 6A–C and caption
Sucrose intake: Second injection 15 min before final sucrose test, four days after NOR injection. Stress-stratified dose analyses were exploratory; both doses partially restored intake in stressed animals. — Experiment 4 results; Figure 6D and caption
CX-516 dose series in stressed and non-stressed rats · Methods: Study design, Experiment 4, NOR test, Intracranial injections, Drugs, Statistical analysis; Results: Antidepressant-like effects of the ampakine CX-516; Figure 6A–D and caption; Discussion limits
Systemic CX516 and hippocampal synaptic physiology
Animal study · Male Tm4sf2−/y and Tm4sf2+/y mice; chronic systemic treatment followed by ex vivo hippocampal CA1 recordings; electrophysiology methods describe 60-day-old mice and three mice per genotype/treatment. [4]
After five days of CX516 treatment, abnormal AMPAR rectification and impaired long-term potentiation in Tm4sf2−/y mice shifted toward wild-type control values. Recording-unit counts are cells or slices, not independent animals. This is an in vivo treatment design with ex vivo endpoints.
Conditions shared by the study groups
- Route
- Intraperitoneal
- Frequency
- Twice daily, morning and evening
- Treatment course
- 3 days vehicle habituation followed by 5 days CX516; last injection 15 h before experiments
- Vehicle
- Saline plus 15–20% 2-hydroxypropyl-beta-cyclodextrin
- Chronic CX516 versus vehicle
- Model: Male Tm4sf2−/y and Tm4sf2+/y mice; 60–90 days in treatment methods
Methods and source locations
Compound reported in the paper: CX516; Compound label in the paper: CX516
Compound-level systemic research; ex vivo endpoints do not establish clinical efficacy or molecular binding kinetics.
Materials and Methods: Animals, Electrophysiology, CX516 Chronic Treatment, Data Analysis; Results: Treatment With the Ampakine CX516 Rescues Synaptic Alterations; Figure 5A–C and caption
AMPAR rectification index, current amplitude at −60 mV divided by +40 mV: Whole-cell CA1 recordings; one-way ANOVA with Newman–Keuls post test; figure annotates *P < 0.05 and **P < 0.01. No comparison-specific exact p values inferred. — Figure 5B; CX516 synaptic rescue results; Electrophysiology
Long-term potentiation of CA1 fEPSP slope: Schaffer collateral stimulation and CA1 stratum radiatum field recording; Figure 5C displays final 10 min; one-way ANOVA followed by Newman–Keuls post test. Multiple slices from mice are not independent animal replicates. — Figure 5C; CX516 synaptic rescue results
Chronic CX516 versus vehicle · Materials and Methods: Animals, Electrophysiology, CX516 Chronic Treatment, Data Analysis; Results: Treatment With the Ampakine CX516 Rescues Synaptic Alterations; Figure 5A–C and caption
