Biology subjects

Ziolkowska, B.

Publications and source records attributed to Ziolkowska, B..

4 recordsLinked to original sources

bioRxiv2025

Decreased social, drug, and food reward sensitivity in adolescent mice

Adolescence shapes adaptive adult behaviors. Most studies compare single adolescent and adult age groups using only one type of reward, limiting insight into developmental trajectories underlying behavioral change. Here, we investigated how social, cocaine, and palatable food rewards become associated with environmental contexts in female and male C57BL/6 mice across early- (pubertal onset), mid- (peripubertal phase), and late- (sexual maturity) adolescence, compared to adults. Using the conditioned place preference (CPP) task, we found that generally all rewards induced place preference for the reward-associated context, with only minor effects of sex. In contrast, age significantly influenced CPP expression. Adolescent mice exhibited a significantly reduced CPP compared to adults in palatable food and social CPP paradigms, evident in both decreased mean conditioned context preference and lower proportion of animals that developed a preference after conditioning. Cocaine CPP was not significantly affected by age. Direct comparisons across CPP task outcomes further confirmed that age, rather than reward type or sex, was the primary factor influencing the magnitude of CPP. Specifically, mid- and late-adolescent mice showed reduced mean reward CPP, and mid-adolescents were less likely to express a reward preference relative to adults. Based on the behavioral analyses, we conclude that the lower expression of preference for a conditioned context in adolescent animals is due to developmental changes in reward sensitivity, rather than deficits in learning or higher novelty-seeking behavior.

animal behavior and cognition↗

bioRxiv2025

Changes in social reward across adolescence in male mice

In humans, adolescence is a time of dynamic behavioral and emotional changes, including a transient decrease in affect associated with being among family members. It is not clear if a similar change occurs in rodent species used to model human psychiatric disorders. Here, we investigated the developmental profile of the rewarding value of interactions with siblings across adolescence in male mice, using the social conditioned place preference task. We found that the reward value of social interactions followed a similar course to that in humans: high in early adolescence, it decreased in mid-adolescence and returned to the initial level in late adolescence. The observed change was specific to social interaction, as no age-dependent changes in preference for cocaine-conditioned context were detected. Taken together, these data show similarities between mice and humans in developmental changes in sensitivity to the rewarding effects of interactions with familiar kin.

neuroscience↗

bioRxiv2024

μ-Opioid receptor transcriptional variants in the murine forebrain and spinal cord

BackgroundOprm1, the gene encoding the -opioid receptor, has multiple reported transcripts, with a variable 3 region and many alternative sequences encoding the C-terminus of the protein. The functional implications of this variability remain mostly unexplored, though a recurring notion is that it could be exploited by developing selective ligands with improved clinical profiles. Here, we comprehensively examined Oprm1 transcriptional variants in the murine central nervous system. MethodsRNA-seq transcription analyses were performed based on Oxford Nanopore Sequencing (ONS) and 10x Genomics Visium spatial transcriptomics data. The spatial distribution of Oprm1 exons was evaluated via RNAscope in situ hybridization. Tissue and cell-type specificity was assessed based on reanalysis single-cell RNAseq databases. ResultsWe detected a mismatch between transcripts annotated in GRCm38/mm10 and RNA-seq results. Sequencing data indicated that the primary Oprm1 transcript has a 3 terminus located on chr10:6,860,027, which is ~9.5 kilobases downstream of the longest annotated exon 4 end. Long-read sequencing confirmed that the final Oprm1 exon included a 10.2 kilobase long 3 untranslated region. The presence of the long variant was unambiguously confirmed using RNAscope in situ hybridization. The long variant was observed in the thalamus, striatum, cortex and spinal cord. Expression of additional variants of the Oprm1 gene was close to the detection limit. Reanalysis of single-cell sequencing data confirmed these observations and indicated that Oprm1 was expressed mainly in parvalbumin-, somatostatin- and VIP-positive cells. ConclusionThe primary transcript of the Oprm1 mouse gene is a variant with a long 3 untranslated region. Author SummaryOpioids are essential for the management of pain and have multiple other medical indications; however, their addictive properties and widespread misuse have led to a severe modern health crisis. Accordingly, there has been a major effort to develop novel compounds that retain clinical effectiveness while diminishing their addictive potential and other adverse effects. One of the potential avenues for safer opioid drugs is developing compounds that are selective for a specific group of the main targets of opioid medications--the -opioid receptors. Multiple variants the -opioid receptor have been reported, encoded by different transcripts of the Oprm1 gene. Here, we used RNA transcript sequencing and in situ hybridization with probes to detect different parts of Oprm1 transcripts to validate the existence of various reported isoforms. Our main finding is that the primary transcript of the receptor is much longer than the current reference sequences annotated in the mouse genome and has an over 10,000-base-long noncoding sequence at the 3 terminus. Several other types of transcripts are also expressed; however, they represent approximately 15% or less of the total transcript content in each of the examined brain regions. In the context of future research on opioid drugs, these results indicate that it is unlikely that different subpopulations of receptors could be targeted.

genomics↗

bioRxiv2023

Mu-opioid receptor-dependent changes in social reward across adolescence in mice

RationaleSocial behaviors undergo dramatic changes during adolescence, enabling the development of adult social abilities. These changes are intricately linked to the development of the brain reward system and the activity of endogenous opioid signaling. However, the involvement of the opioid system in the development of social behaviors still raises more questions than answers. ObjectivesHere, we investigated the role of the endogenous opioid system in the rewarding effects of social contact in early and late adolescent male mice. MethodsSocial reward was assessed using the social conditioned place preference task in early adolescent (~34 days old) and late adolescent (~41 days old) male mice that received a single dose of the selective opioid receptor antagonists cyprodime (1 mg/kg, i.p.), naltrindole (1 mg/kg, i.p.) or norbinaltorphimine (10 mg/kg, i.p.) before the preference posttest. ResultsThe administration of cyprodime or naltrindole before the posttest significantly increased the preference for the social-conditioned context in early but not late adolescent mice. In contrast, pretreatment with norbinaltorphimine had no effect on context preference. ConclusionsOur findings support a modified version of the state-dependent mu-opioid receptor model of social behavior, where the effects of opioid ligands are not reversed during development but rather weaken or disappear with age. Furthermore, the results indicate that interactions with siblings in early adolescent mice are motivated by negative reinforcement, whereas those in late adolescence are motivated by positive reinforcement.

neuroscience↗