Establishment of a social conditioned place preference paradigm for the study of social reward in female mice.
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ABSTRACT:
SUBMITTER: Harda Z
PROVIDER: S-EPMC9253334 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:AimsG protein-activated inwardly rectifying potassium (GIRK) channels are related to rewarding effects of addictive drugs. The GIRK2 subunit is thought to play key roles in the reward system. Weaver mutant mice exhibit abnormal GIRK2 function and different behaviors that are caused by several addictive substances compared with wild-type mice. However, mechanisms of reward-related alterations in weaver mutant mice remain unclear. The present study investigated changes in the rewarding effects of methamphetamine (METH) in weaver mutant mice.MethodsThe rewarding effects of METH (4.0 mg/kg) were investigated using the conditioned place preference (CPP) paradigm. Extracellular dopamine level in the nucleus accumbens (NAc) was measured by in vivo microdialysis. To identify brain regions that were associated with these changes in rewarding effects, METH-induced alterations of Fos expression were investigated by immunohistochemical analysis.ResultsWeaver mutant mice exhibited a significant decrease in METH-induced CPP and dopamine release in the NAc. Methamphetamine significantly increased Fos expression in the posterior NAc (pNAc) shell in wild-type but not in weaver mutant mice.ConclusionsMethamphetamine did not induce rewarding effects in weaver mutant mice. The pNAc shell exhibited a significant difference in neuronal activity between wild-type and weaver mutant mice. The present results suggest that the absence of METH-induced CPP in weaver mutant mice is probably related to an innate reduction of dopamine and decreased neural activity in the pNAc shell that is partially attributable to the change of GIRK channel function. GIRK channels, especially those containing the GIRK2 subunit, appear to be involved in METH dependence.
| S-EPMC7722684 | biostudies-literature
Project description:Gut microbiota has been found to establish a bidirectional relationship with the central nervous system. Variations of the gut microbiota has been implicated in various mental disorders, including opioid use disorders. Morphine exposure has been repeatedly found to disrupt the gut microbiota, but association between the gut microbiota and the sensitivity to morphine reward remains unknown. In this study the conditioned place preference (CPP) paradigm was used for morphine-treated rats and saline-treated rats. After the CPP procedure, the morphine-treated rats were divided equally into the low and high CPP (L- and H-CPP) groups according to the CPP scores. We adopted 16S rRNA sequencing for the fecal bacterial communities at baseline and post-conditioning. By comparing the morphine-treated group with saline-treated group, we found alterations of microbial composition in the morphine-treated group, but no significant differences in alpha diversity. The L-CPP group and H-CPP group differed in microbial composition both before and after morphine treatment. The relative abundance of certain taxa was correlated to the CPP scores, such as Alloprevotella and Romboutsia. This study provides direct evidence that morphine exposure alters the composition of the gut microbiota in rats and that microbial alterations are correlated to the sensitivity to morphine reward. These findings may help develop novel therapeutic and preventive strategies for opioid use disorder.
| S-EPMC7484999 | biostudies-literature
Project description:Endogenous opioids have been implicated in cocaine reward. However, the role of each opioid peptide in this regard is unknown. Notably, the role of each peptide in extinction and reinstatement is not fully characterized. Thus, we assessed whether cocaine-induced conditioned place preference (CPP) and its extinction and reinstatement would be altered in the absence of beta-endorphin. We also examined if sex-related differences would exist in these processes. Male and female mice lacking beta-endorphin and their respective controls were tested for baseline place preference on day 1. On day 2, mice were treated with saline/cocaine (15 mg/kg) and confined to the vehicle- or drug-paired chamber for 30 min, respectively. In the afternoon, mice were treated with the alternate treatment and confined to the opposite chamber. Mice were then tested for CPP on day 3. Mice then received additional conditioning on this day as well as on day 4. Mice were then tested for CPP on day 5. Mice then received extinction training on day 9. On day 10, mice were tested for extinction and then reinstatement of CPP following a priming dose of cocaine (7.5 mg/kg). Male and female mice lacking beta-endorphin did not exhibit CPP following single conditioning with cocaine. On the other hand, only male mice lacking beta-endorphin failed to show CPP after repeated conditioning. Nonetheless, reinstatement of CPP was blunted in both male and female mice lacking beta-endorphin compared to controls. The present results suggest that beta-endorphin plays a functional role in cocaine-induced CPP and its reinstatement, and sex-related differences exist in the regulatory action of beta-endorphin on the acquisition but not reinstatement of cocaine CPP.
| S-EPMC8702804 | biostudies-literature
Project description:Patients suffering from opioid use disorder often relapse during periods of abstinence, which is posited to be caused by negative affective states that drive motivated behaviors. Here, we explored whether conditioning mice with morphine in a conditioned place preference (CPP) training paradigm evoked anxiety-like behavior during morphine abstinence. To do this, mice were conditioned with morphine (10 mg/kg, i.p.) for 5 days. Twenty-four hours following conditioning, anxiety levels were tested by measuring time in the open arms of the elevated plus-maze. The next day, mice were placed in the three-compartment chamber to measure morphine-induced CPP. Our results show that following morphine conditioning, mice spent significantly less time in the open arm of the elevated plus-maze and expressed robust morphine CPP on CPP test day. Furthermore, we found that an acute treatment with (R,S)-ketamine (10 mg/kg, i.p.), a medication demonstrating promise for preventing anxiety-related phenotypes, 30 min before testing on post-conditioning day 1, increased time spent in the open arm of the elevated plus-maze in saline- and morphine-conditioned mice. Additionally, we found that the second injection of ketamine 30 min before CPP tests on post-conditioning day 2 prevented morphine-induced CPP, which lasted for up to 28 days post-conditioning. Furthermore, we found that conditioning mice with 10% (w/v) sucrose using an oral self-administration procedure did not evoke anxiety-like behavior, but elicited robust CPP, which was attenuated by ketamine treatment 30 min before CPP tests. Overall, our results suggest that the ketamine-induced block of morphine CPP may not be attributed solely to alleviating negative affective states, but potentially through impaired memory of morphine-context associations.
| S-EPMC7253643 | biostudies-literature
Project description:The relationship between stress and drug use is well demonstrated. Stress-induced by repeated social defeat (RSD) enhances the conditioned place preference (CPP) induced by cocaine in mice. The phenomenon of resilience understood as the ability of subjects to overcome the negative effects of stress is the focus of increasing interest. Our aim is to characterize the behavior of resilient animals with respect to the effects of RSD on the CPP induced by cocaine. To this end, 25 male C57BL/6 mice were exposed to stress by RSD during late adolescence, while other 15 male mice did not undergo stress (controls). On the 2 days following the last defeat, all the animals carried out the elevated plus maze (EPM) and Hole Board, Social Interaction, Tail Suspension and Splash tests. Three weeks later, all the animals performed the CPP paradigm with a low dose of cocaine (1 mg/kg). Exposure to RSD decreased all measurements related to the open arms of the EPM. It also reduced social interaction, immobility in the tail suspension test (TST) and grooming in the splash test. RSD exposure also increased the sensitivity of the mice to the rewarding effects of cocaine, since only defeated animals acquired CPP. Several behavioral traits were related to resilience to the potentiating effect of RSD on cocaine CPP. Mice that showed less submission during defeat episodes, a lower percentage of time in the open arms of the EPM, low novelty-seeking, high social interaction, greater immobility in the TST and a higher frequency of grooming were those that were resilient to the long-term effects of social defeat on cocaine reward since they behaved like controls and did not develop CPP. These results suggest that the behavioral profile of resilient defeated mice is characterized by an active coping response during episodes of defeat, a greater concern for potential dangers, less reactivity in a situation of inevitable moderate stress and fewer depressive-like symptoms after stress. Determining the neurobehavioral substrates of resilience is the first step towards developing behavioral or pharmacological interventions that increase resilience in individuals at a high risk of suffering from stress.
| S-EPMC6962131 | biostudies-literature
Project description:Drug-induced alterations in gene expression play an important role in the development of addictive behavior. Methionine has been proven to inhibit addictive behaviors of cocaine dependence. However, the mechanisms underlying how methionine use corresponds to drug-induced behaviors still remain unclear. We performed mRNA and miRNA high-throughput sequencing of the prefrontal cortex in a mouse model of cocaine CPP combined with L-methionine in order to identify L-methionine target miRNAs and genes that participate in the cocaine conditioned place preference (CPP). We found that the L-methionine inhibits cocaine CPP. Sequencing data analysis showed that L-methionine down-regulates genes enriched in the Glutamatergic Synapse pathways and significantly reversed the cocaine-induced expression changes of the substance dependence pathways (Morphine addiction and Nicotine addiction) and the neurotransmitter synapse pathways (Glutamatergic Synapse, Cholinergic Synapse and GABAergic Synapse). Furthermore, the Glutamatergic synapse was either overlapped between DEGs with DEGs-miRNA induced by cocaine CPP, or with the MET effects on cocaine CPP. Nineteen targeted genes were investigated and five were identified (Gria4, Grid1, Grik4, Grik5 and Grin3a) to belong to iGluR family. Interestingly, there were several miRNAs that had the same sequence which targets the iGluR family: Mmu-miR-30e-50p and mmu-miR-380-5p share UUGAC motif and targets Grik4; mmu-miR-6940-3p and mmu-miR-212-5p both share UGGCU motif which targets Gria4 and Grid1 respectively. Thus, we demonstrated the efficacy of L-methionine in counteracting the effects of cocaine CPP and identified specific genes of synaptic plasticity pathways, especially the Glutamatergic synapse pathway, which is modulated by L-methionine in response to cocaine dependence.
2020-03-10 | GSE146631 | GEO
Project description:We recently developed a conditioned place preference (CPP) procedure, commonly used to study rewarding drug effects, to demonstrate that dominant sexually-experienced CD-1 male mice form CPP to contexts previously associated with defeating subordinate male C57BL/6J mice. Here we further characterized conditioned and unconditioned aggression behavior in CD-1 mice. In Exp. 1 we used CD-1 mice that displayed a variable spectrum of unconditioned aggressive behavior toward younger subordinate C57BL/6J intruder mice. We then trained the CD-1 mice in the CPP procedure where one context was intruder-paired, while a different context was not. We then tested for aggression CPP 1 day after training. In Exp. 2, we tested CD-1 mice for aggression CPP 1 day and 18 days after training. In Exp. 3-4, we trained the CD-1 mice to lever-press for palatable food and tested them for footshock punishment-induced suppression of food-reinforced responding. In Exp. 5, we characterized unconditioned aggression in hybrid CD-1 × C57BL/6J D1-Cre or D2-Cre F1 generation crosses. Persistent aggression CPP was observed in CD-1 mice that either immediately attacked C57BL/6J mice during all screening sessions or mice that gradually developed aggressive behavior during the screening phase. In contrast, CD-1 mice that did not attack the C57BL/6J mice during screening did not develop CPP to contexts previously paired with C57BL/6J mice. The aggressive phenotype did not predict resistance to punishment-induced suppression of food-reinforced responding. CD-1 × D1-Cre or D2-Cre F1 transgenic mice showed strong unconditioned aggression. Our study demonstrates that aggression experience causes persistent CPP and introduces transgenic mice for circuit studies of aggression.
| S-EPMC5243174 | biostudies-literature
Project description:Relapse to smoking occurs at higher rates in women compared with men, especially when triggered by stress. Studies suggest that sex-specific interactions between nicotine reward and stress contribute to these sex differences. Accordingly, novel treatment options targeting stress pathways, such as guanfacine, an α2-adrenergic receptor agonist, may provide sex-sensitive therapeutic effects. Preclinical studies are critical for elucidating neurobiological mechanisms of stress-induced relapse and potential therapies, but rodent models of nicotine addiction are often hindered by large behavioral variability. In this study, we used nicotine conditioned place preference to investigate stress-induced reinstatement of nicotine preference in male and female mice, and the effects of guanfacine on this behavior. Our results showed that overall, nicotine induced significant place preference acquisition and swim stress-induced reinstatement in both male and female mice, but with different nicotine dose-response patterns. In addition, we explored the variability in nicotine-dependent behaviors with median split analyses and found that initial chamber preference in each sex differentially accounted for variability in stress-induced reinstatement. In groups that showed significant stress-induced reinstatement, pretreatment with guanfacine attenuated this behavior. Finally, we evaluated neuronal activation by Arc immunoreactivity in the infralimbic cortex, prelimbic cortex, anterior insula, basolateral amygdala, lateral central amygdala and nucleus accumbens core and shell. Guanfacine induced sex-dependent changes in Arc immunoreactivity in the infralimbic cortex and anterior insula. This study demonstrates sex-dependent relationships between initial chamber preference and stress-induced reinstatement of nicotine conditioned place preference, and the effects of guanfacine on both behavior and neurobiological mechanisms.
| S-EPMC8045136 | biostudies-literature
Project description:Several personality factors have been implicated in vulnerability to addiction by impacting learning and decision making. One such factor is intolerance of uncertainty (IU), the tendency to perceive uncertain situations negatively and avoid them. Conditioned place preference (CPP), which compares preference for contexts paired with reward, has been used to examine the motivation for both drug and non-drug rewards. However, preference for locations associated with non-drug reward, as well as the potential influence of IU, has not been thoroughly studied in individuals with addiction. In the current study, we examined CPP using a computer-based task in a sample of addicted individuals undergoing opioid maintenance treatment and never-addicted controls. Patients were confirmed to have higher IU than controls. In the CPP task, the two groups did not differ in overall time spent in the previously-rewarded context. However, controls were more likely than patients to immediately return to this context. Contrary to our predictions, IU was not a significant predictor of preference for the previously-rewarded context, although higher IU in controls was associated with a higher number of rewards obtained in the task. No such relationship was found in patients.
| S-EPMC5967368 | biostudies-literature
Project description:RATIONALE:Previous work has shown that some mouse strains (e.g., DBA/2J [D2]) readily develop robust ethanol-induced conditioned place preference (CPP) while others (e.g., C57BL/6J [B6]) do not. Though commonly interpreted as a difference between strains in sensitivity to ethanol reward, other explanations for this finding are possible. OBJECTIVES:To explore the hypothesis that variation in sensitivity to contextual cues underlies CPP differences, the present work investigated ethanol-induced CPP in D2 and B6 mice trained with a standard tactile (floor) cue procedure compared to mice trained with tactile plus visual-spatial cues. METHODS:In an unbiased CPP procedure, mice were assigned to either a single element cue (one-compartment apparatus with tactile cue presented in the dark) or multi-modal cues (two-compartment apparatus with distinct tactile floors and lights on). To track CPP development, mice received preference tests during training in addition to a final test. RESULTS:Adding visual-spatial cues accelerated CPP acquisition in both D2 and B6 mice. However, this enhancement was observed after just one ethanol-conditioning trial in D2 mice, but was observed only after four ethanol-conditioning trials in B6 mice. Differences between groups trained with single or multi-modal cues disappeared as conditioning reached asymptote, with D2 mice showing a more rapid loss of the effect and a higher maximum CPP. CONCLUSIONS:Although multi-modal cues produce more rapid conditioning, their inability to reduce or eliminate strain differences in CPP supports the interpretation that these strains differ in their sensitivity to ethanol reward.
| S-EPMC6298874 | biostudies-literature