Inhibition of Nitric Oxide Synthesis Prevents the Effects of Intermittent Social Defeat on Cocaine-Induced Conditioned Place Preference in Male Mice
Abstract
:1. Introduction
2. Results
2.1. Behavioural Analysis during Episodes of Defeat
2.2. Role of 7-NI in the Short-Term Effects of ISD
2.3. Role of 7-NI in the Long-Term Effects of ISD
2.4. Correlations between Behavioural Measurements
3. Discussion
4. Materials and Methods
4.1. Subjects
4.2. Drugs
4.3. Experimental Protocols
4.3.1. Intermittent Social Defeat (ISD)
4.3.2. Elevated Plus Maze (EPM)
4.3.3. Social Interaction Test
4.3.4. Object Recognition Test (ORT)
4.3.5. Tail Suspension Test (TST)
4.3.6. Conditioned Place Preference (CPP)
4.4. Experimental Design
4.5. Statistical Analyses
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Data Availability Statement
Conflicts of Interest
References
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Experimental Animals | Avoidance/ Flee | Latency Avoid/Flee | Defence/ Submission | Latency Defence/Subm. | ||||
Encounter | 1 | 4 | 1 | 4 | 1 | 4 | 1 | 4 |
Defeated mice treated with VEH | 117.39 | 168.72 | [26.52 | 5.15] | 15.64 | 20.86 | 40.71 | 73.2 |
(n = 10) | ±31.24 | ±22.61 | ±13.71 | ±1.53 | ±3.23 | ±5.38 | ±17.17 | ±34.82 |
Defeated mice treated with 7-NI7 | 142.87 | 155.49 | 4.64 | 4.32 | 9.5 | 15.39 | 74.67 | 37.86 |
(n = 12) | ±20.28 | ±21.24 | ±2.07 | ±1.31 | ±2.43 | ±3.89 | ±27.12 | ±12.81 |
Defeated mice treated with 7-NI12 | 96.5 | 125.21 | [2.69 | 2.67] * | 14.27 | 17.54 | 65.84 | 31.75 |
(n = 12) | ±17.73 | ±24.63 | ±0.55 | ±0.91 | ±4.32 | ±3.38 | ±26.53 | ±12.03 |
Aggressive Opponents | Threat | Latency Threat | Attack | Latency Attack | ||||
Encounter | 1 | 4 # | 1 | 4 | 1 | 4 | 1 | 4 |
Confronted with VEH-treated mice | [15.89 | 10.32] | 23.48 | 43.56 | 40.96 | 36.47 | 22.28 | 6.98 |
(n = 10) | ±2.77 | ±2.17 | ±13.26 | ±19.25 | ±5.18 | ±7.7 | ±12.79 | ±2.06 |
Confronted with 7-NI7 treated mice | 14.01 | 8.32 | 15.26 | 25.39 | 35.1 | 29.09 | 3.78 | 3.73 |
(n = 12) | ±3.33 | ±1.84 | ±7.1 | ±9.93 | ±3.69 | ±2.9 | ±0.98 | ±1.12 |
Confronted with 7-NI12 treated mice | [6.84 | 6.4] * | 22.46 | 41.32 | 31.18 | 26.04 | 2.67 | 4.6 |
(n = 12) | ±1.53 | ±1.59 | ±8.35 | ±15.65 | ±4.35 | ±5.22 | ±0.55 | ±2.27 |
Threat 1 | Threat 4 | LThreat 1 | LThreat 4 | LAttack 1 | Av/Flee 1 | Av/Flee 4 | LAv/Flee 1 | LAv/Flee 4 | Def/S 1 | Def/S 4 | LDef/S 1 | LDef/S 4 | |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Threat 1 | ns | ns | ns | ns | r = −0.357; R2 = 0.127 | ns | ns | ns | ns | ns | ns | ns | |
Threat 4 | ns | ns | ns | ns | ns | r = −0.444; R2 = 0.197 | ns | ns | ns | r = 0.613; R2 = 0.375 | ns | ns | |
LThreat 1 | ns | ns | ns | r = 0.638; R2 = 0.407 | ns | ns | r = 0.58; R2 = 0.336 | ns | ns | ns | r = 0.461; R2 = 0.213 | ns | |
LThreat 4 | ns | ns | ns | ns | ns | ns | ns | ns | ns | r = −0.357; R2 = 0.128 | ns | r = 0.516; R2 = 0.266 | |
LAttack 1 | ns | ns | 0.001 | ns | ns | ns | r = 0.937; R2 = 0.879 | ns | ns | ns | ns | ns | |
Av/Flee 1 | 0.05 | ns | ns | ns | ns | ns | r = −0.36; R2 = 0.129 | ns | r = −0.458; R2 = 0.210 | ns | ns | ns | |
Av/Flee 4 | ns | 0.01 | ns | ns | ns | ns | ns | ns | ns | r = −0.731; R2 = 0.535 | ns | r = 0.423; R2 = 0.179 | |
LAv/Flee 1 | ns | ns | 0.001 | ns | 0.01 | 0.05 | ns | ns | ns | ns | ns | ns | |
LAv/Flee 4 | ns | ns | ns | ns | ns | ns | ns | ns | ns | ns | ns | ns | |
Def/S 1 | ns | ns | ns | ns | ns | 0.01 | ns | ns | ns | ns | r = −0.498; R2 = 0.248 | ns | |
Def/S 4 | ns | 0.001 | ns | 0.05 | ns | ns | 0.01 | ns | ns | ns | ns | r = −0.485; R2 = 0.235 | |
LDef/S 1 | ns | ns | 0.01 | ns | ns | ns | ns | ns | ns | 0.01 | ns | ns | |
LDef/S 4 | ns | ns | ns | 0.01 | ns | ns | 0.05 | ns | ns | ns | 0.01 | ns |
Threat 1 | Attack 1 | Attack 4 | LAttack 1 | Av/Flee 4 | LAv/Flee 1 | Def/S 4 | Immob | LImmob | TOA | %TOA | EOA | %EOA | ISI | CPP | |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Threat 1 | ns | ns | ns | ns | ns | ns | ns | ns | ns | ns | ns | ns | r = −0.356; R2 = 0.126 | ns | |
Attack 1 | ns | ns | ns | ns | ns | ns | ns | ns | r = 0.361; R2 = 0.130 | r = 0.371; R2 = 0.137 | r = 0.361; R2 = 0.130 | ns | ns | ns | |
Attack 4 | ns | ns | ns | ns | ns | ns | ns | ns | r = 0.401; R2 = 0.161 | r = 0.363; R2 = 0.131 | ns | r = 0.342; R2 = 0.117 | r = 0.369; R2 = 0.136 | ns | |
LAttack 1 | ns | ns | ns | ns | r = 0.937; R2 = 0.879 | ns | ns | r = 0.507; R2 = 0.257 | ns | ns | ns | ns | ns | ns | |
Av/Flee 4 | ns | ns | ns | ns | ns | r = −0.731; R2 = 0.535 | ns | ns | r = 0.366; R2 = 0.134 | ns | ns | ns | ns | ||
LAv/Flee 1 | ns | ns | ns | 0.001 | ns | ns | ns | r = 0.475; R2 = 0.225 | ns | ns | ns | ns | ns | ns | |
Def/S 4 | ns | ns | ns | ns | 0.001 | ns | r = 0.345; R2 = 0.119 | ns | r = −0.496; R2 = 0.246 | r = −0.431; R2 = 0.186 | r = −0.424; R2 = 0.179 | ns | ns | r = 0.371; R2 = 0.138 | |
Immob | ns | ns | ns | ns | ns | ns | 0.05 | ns | ns | ns | ns | ns | r = 0.443; R2 = 0.196 | ns | |
L Immob | ns | ns | ns | 0.01 | ns | 0.01 | ns | ns | ns | ns | ns | ns | ns | ns | |
TOA | ns | 0.05 | 0.05 | ns | 0.05 | ns | 0.01 | ns | ns | r = 0.96; R2 = 0.922 | r = 0.878; R2 = 0.771 | r = 0.821; R2 = 0.674 | ns | ns | |
%TOA | ns | 0.05 | 0.05 | ns | 0.05 | ns | 0.05 | ns | ns | 0.001 | r = 0.852; R2 = 0.725 | r = 0.888; R2 = 0.788 | ns | ns | |
EOA | ns | 0.05 | ns | ns | ns | ns | 0.05 | ns | ns | 0.001 | 0.001 | r = 0.825; R2 = 0.681 | r = −0.381; R2 = 0.145 | ns | |
%EOA | ns | ns | 0.05 | ns | ns | ns | ns | ns | ns | 0.001 | 0.001 | 0.001 | ns | ns | |
ISI | 0.05 | ns | 0.05 | ns | ns | ns | ns | 0.01 | ns | ns | ns | 0.05 | ns | ns | |
CPP | ns | ns | ns | ns | ns | ns | 0.05 | ns | ns | ns | ns | ns | ns | ns |
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Martínez-Caballero, M.Á.; García-Pardo, M.P.; Calpe-López, C.; Arenas, M.C.; Manzanedo, C.; Aguilar, M.A. Inhibition of Nitric Oxide Synthesis Prevents the Effects of Intermittent Social Defeat on Cocaine-Induced Conditioned Place Preference in Male Mice. Pharmaceuticals 2024, 17, 1203. https://doi.org/10.3390/ph17091203
Martínez-Caballero MÁ, García-Pardo MP, Calpe-López C, Arenas MC, Manzanedo C, Aguilar MA. Inhibition of Nitric Oxide Synthesis Prevents the Effects of Intermittent Social Defeat on Cocaine-Induced Conditioned Place Preference in Male Mice. Pharmaceuticals. 2024; 17(9):1203. https://doi.org/10.3390/ph17091203
Chicago/Turabian StyleMartínez-Caballero, María Ángeles, María Pilar García-Pardo, Claudia Calpe-López, María Carmen Arenas, Carmen Manzanedo, and María Asuncion Aguilar. 2024. "Inhibition of Nitric Oxide Synthesis Prevents the Effects of Intermittent Social Defeat on Cocaine-Induced Conditioned Place Preference in Male Mice" Pharmaceuticals 17, no. 9: 1203. https://doi.org/10.3390/ph17091203