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Journal: bioRxiv

Article Title: Effects of serotonin agonists LSD and 25CN-NBOH on conditioned place preference and on synaptic plasticity of VTA dopamine neurons in mice

doi: 10.1101/2024.12.12.628157

Figure Lengend Snippet:

Article Snippet: The conditioned place preference behaviour was studied with C57BL/6JCrl (JAX® Mice Strain, Charles River, Wilmington, MA, USA) male (n=156) and female (n=32) mice, approximately 8–10 weeks of age at the time of the experimentation, received straight from the supplier, and housed in groups of 4 in reversed 12:12 h light cycle (lights off at 06.00 am).

Techniques: Conditioned Place Preference, Transformation Assay

The initial conditioned place preference experiment CPP1 indicated that 3.0 mg/kg 25CN-NBOH would induce conditioned place preference (A) as measured by the within-treatment Floor subgroup difference in the time spent on the Grid. This was also reflected to an extent by increases, although statistically non-significant, in the time spent on the drug-paired side of the apparatus before and after the conditioning (D, G). Replication of the experiment, CPP2, failed to show the same effect; there all the treatments showed a difference between the Floor subgroups with statistically significant effect in 0.2 mg/kg LSD treatment group (B). However, there were no observable changes in the time spent on the drug-paired side in any of the treatment groups (E, F). Pooling the results together maintained the statistically significant differences in the Floor subgroup analysis with both LSD and 25CN-NBOH (C), but the time-shift analysis showed more neutral results (F, I). Data shown as means (bars in A–C; black circles G–I) with 95% confidence intervals (black error bars A–C and G–I) or as individual values (circles A–C; lines D–F). In G–I the paired mean difference is plotted with a bootstrap sampling distribution. * p<0.05, ** p<0.01 difference between the time on Grid between the Grid and Hole subgroups within a treatment group.

Journal: bioRxiv

Article Title: Effects of serotonin agonists LSD and 25CN-NBOH on conditioned place preference and on synaptic plasticity of VTA dopamine neurons in mice

doi: 10.1101/2024.12.12.628157

Figure Lengend Snippet: The initial conditioned place preference experiment CPP1 indicated that 3.0 mg/kg 25CN-NBOH would induce conditioned place preference (A) as measured by the within-treatment Floor subgroup difference in the time spent on the Grid. This was also reflected to an extent by increases, although statistically non-significant, in the time spent on the drug-paired side of the apparatus before and after the conditioning (D, G). Replication of the experiment, CPP2, failed to show the same effect; there all the treatments showed a difference between the Floor subgroups with statistically significant effect in 0.2 mg/kg LSD treatment group (B). However, there were no observable changes in the time spent on the drug-paired side in any of the treatment groups (E, F). Pooling the results together maintained the statistically significant differences in the Floor subgroup analysis with both LSD and 25CN-NBOH (C), but the time-shift analysis showed more neutral results (F, I). Data shown as means (bars in A–C; black circles G–I) with 95% confidence intervals (black error bars A–C and G–I) or as individual values (circles A–C; lines D–F). In G–I the paired mean difference is plotted with a bootstrap sampling distribution. * p<0.05, ** p<0.01 difference between the time on Grid between the Grid and Hole subgroups within a treatment group.

Article Snippet: The conditioned place preference behaviour was studied with C57BL/6JCrl (JAX® Mice Strain, Charles River, Wilmington, MA, USA) male (n=156) and female (n=32) mice, approximately 8–10 weeks of age at the time of the experimentation, received straight from the supplier, and housed in groups of 4 in reversed 12:12 h light cycle (lights off at 06.00 am).

Techniques: Conditioned Place Preference, Sampling

Further analysis of the conditioned place preference with additional doses and morphine as a positive control (CPP3 panels ACE, and CPP4, panels BDF) showed no statistically significant differences between the Floor subgroups with any of the used doses of the serotonergic agents (A, B). Analysing the change in the time spent on the drug-paired side revealed statistically significant increases in the morphine-treated groups in both experiments (C, D), but not with the other treatments. The 1.5 mg/kg 25CN-NBOH showed similar increases in the time spent on the drug-paired floor as morphine (D, F) but the difference did not reach the set significance level. Data shown as means (bars in A–B; black circles E–F) with 95% confidence intervals (black error bars A–B and E–F) or as individual values (circles A–C; lines C–D). In E and F, the paired mean difference is plotted with a bootstrap sampling distribution. * p<0.05 difference between the Grid and Hole subgroups within a treatment group. # p<0.05 paired permutation t-test between the time on drug-paired side on the habituation and the test sessions.

Journal: bioRxiv

Article Title: Effects of serotonin agonists LSD and 25CN-NBOH on conditioned place preference and on synaptic plasticity of VTA dopamine neurons in mice

doi: 10.1101/2024.12.12.628157

Figure Lengend Snippet: Further analysis of the conditioned place preference with additional doses and morphine as a positive control (CPP3 panels ACE, and CPP4, panels BDF) showed no statistically significant differences between the Floor subgroups with any of the used doses of the serotonergic agents (A, B). Analysing the change in the time spent on the drug-paired side revealed statistically significant increases in the morphine-treated groups in both experiments (C, D), but not with the other treatments. The 1.5 mg/kg 25CN-NBOH showed similar increases in the time spent on the drug-paired floor as morphine (D, F) but the difference did not reach the set significance level. Data shown as means (bars in A–B; black circles E–F) with 95% confidence intervals (black error bars A–B and E–F) or as individual values (circles A–C; lines C–D). In E and F, the paired mean difference is plotted with a bootstrap sampling distribution. * p<0.05 difference between the Grid and Hole subgroups within a treatment group. # p<0.05 paired permutation t-test between the time on drug-paired side on the habituation and the test sessions.

Article Snippet: The conditioned place preference behaviour was studied with C57BL/6JCrl (JAX® Mice Strain, Charles River, Wilmington, MA, USA) male (n=156) and female (n=32) mice, approximately 8–10 weeks of age at the time of the experimentation, received straight from the supplier, and housed in groups of 4 in reversed 12:12 h light cycle (lights off at 06.00 am).

Techniques: Conditioned Place Preference, Positive Control, Sampling

The biased conditioned placed preference experiments (CPP5 panels ACE, and CPP6 panels BDE) showed LSD to cause mild positive time-shifts (A) and slightly more pronounced in the 25CN-NBOH–treated groups (B). From the serotonin agonists, the 1.5 mg/kg 25CN-NBOH caused a statistically significant increase with a time-shift on the similar level as morphine (B, D). In the CPP5, all the treatment groups tended to increase their time spent on the drug-paired floor (E), whereas this was observable only with the 1.5 mg/kg dose of 25CN-NBOH and the positive control morphine in CPP6 (F). Data shown as means (the gap between the bars A–B; black circles C–D) with 95% confidence intervals (bars A–D) or as individual values (dots A–B; lines E–F). In C and D, the unpaired mean difference against saline is plotted with a bootstrap sampling distribution. * p<0.05 Holm corrected pairwise comparison against the saline group time-shift; # p<0.05, ## p<0.01 ### p<0.0001 paired permutation t-test between the time on drug-paired floor on the pre-test and the test sessions.

Journal: bioRxiv

Article Title: Effects of serotonin agonists LSD and 25CN-NBOH on conditioned place preference and on synaptic plasticity of VTA dopamine neurons in mice

doi: 10.1101/2024.12.12.628157

Figure Lengend Snippet: The biased conditioned placed preference experiments (CPP5 panels ACE, and CPP6 panels BDE) showed LSD to cause mild positive time-shifts (A) and slightly more pronounced in the 25CN-NBOH–treated groups (B). From the serotonin agonists, the 1.5 mg/kg 25CN-NBOH caused a statistically significant increase with a time-shift on the similar level as morphine (B, D). In the CPP5, all the treatment groups tended to increase their time spent on the drug-paired floor (E), whereas this was observable only with the 1.5 mg/kg dose of 25CN-NBOH and the positive control morphine in CPP6 (F). Data shown as means (the gap between the bars A–B; black circles C–D) with 95% confidence intervals (bars A–D) or as individual values (dots A–B; lines E–F). In C and D, the unpaired mean difference against saline is plotted with a bootstrap sampling distribution. * p<0.05 Holm corrected pairwise comparison against the saline group time-shift; # p<0.05, ## p<0.01 ### p<0.0001 paired permutation t-test between the time on drug-paired floor on the pre-test and the test sessions.

Article Snippet: The conditioned place preference behaviour was studied with C57BL/6JCrl (JAX® Mice Strain, Charles River, Wilmington, MA, USA) male (n=156) and female (n=32) mice, approximately 8–10 weeks of age at the time of the experimentation, received straight from the supplier, and housed in groups of 4 in reversed 12:12 h light cycle (lights off at 06.00 am).

Techniques: Positive Control, Saline, Sampling, Comparison