Wyniki wyszukiwania - Biblioteka Nauki

Nowa wersja platformy, zawierająca wyłącznie zasoby pełnotekstowe, jest już dostępna.
Przejdź na https://bibliotekanauki.pl

Ograniczanie wyników

2 Acta Neurobiologiae Experimentalis

2 2017

Znaleziono wyników: 2

Liczba wyników na stronie

Wyniki wyszukiwania

Sortuj według:

Ogranicz wyniki do:

The role of astrocytic glucocorticoid receptor in behavioral effects of opioids

100%

Kudla L. , Skupio U. , Marut L. , Tertil M. , Wawrzczak-Bargiela A. , Przewlocki R.

nr Suppl.1

INTRODUCTION: Glucocorticoid receptor (GR)-dependent mechanisms are considered to affect behavioral effects of multiple drugs of abuse, including opioids. Recent evidence points to the important role of astrocytes in mediating GR-dependent effects in the brain. However, the exact mechanisms of astrocytic GR contribution to behavioral response to opioids remain unknown. AIM(S): Here, we aimed to evaluate effects of opioid receptors ligands in astrocytic GR knockout mice. We assessed the animals in nociception and addiction assays. METHOD(S): We used transgenic mice in which GR is selectively ablated in astrocytes expressing connexin 30 (C×30×GR flox/flox) and non‑transgenic littermates. To investigate nociceptive sensitivity and morphine-induced analgesia, animals were assessed in tail flick test. To evaluate addiction-like behavior, morphine tolerance and naloxone-precipitated morphine withdrawal symptoms were measured. Moreover, sensitivity to opioid reward was tested in conditioned place preference (CPP) paradigm and response to aversive properties of naloxone was measured using conditioned place aversion (CPA) test. RESULTS: Mutant and control mice presented similar nociceptive sensitivity, did not differ in morphine analgesia, developed similar opioid tolerance and morphine-induced CPP. However, when subjected to naloxone-precipitated morphine withdrawal, mutants showed decreased number of jumps, indicating attenuated physical signs of opioid withdrawal. What is more, astrocytic GR knockout mice did not acquire naloxone-induced CPA, suggesting alternations in behavioral response to naloxone-evoked aversion. CONCLUSIONS: Our data indicate that astrocytic GR may be involved in regulation of naloxone-induced aversion and morphine withdrawal. However, knockout of GR in astrocytes does not influence pain sensitivity, morphine analgesia, tolerance and reward-associated memory. In conclusion, our results shed a light on the causal role of GR-dependent signaling in astrocytes in mediating behavioral effects of opioids. FINANCIAL SUPPORT: Funding for this study was provided by Polish National Science Centre Grant: 2013/08/A/ NZ3/00848.

Molecular biomarkers of addiction in a model of long-term morphine self-administration in mice

100%

Skupio U. , Sikora M. , Korostynski M. , Wawrzczak-Bargiela A. , Piechota M. , Przewlocki R.

nr Suppl.1

INTRODUCTION: Chronic exposure to opioids induces various adaptations in brain physiology that lead to formation of dependence and addiction. Commonly used approaches for modeling morphine dependence, such as conditioned place preference and morphine self-administration typically last less than two weeks, which is presumably too short to observe long-lasting alterations in the brain that accompany drug addiction. AIM(S): In the present study, we aimed to establish a novel model of long-term morphine self-administration in C57BL/6J mice. Our second goal was to identify molecular biomarkers, specific transcriptional patterns and signs of genetic predispositions to opiate addiction. METHOD(S): We used automated IntelliCage system to observe the animals in groups. The animals in two separate cages were allowed access to morphine or saccharin solutions for 3 months. We tested animals for symptoms of addiction using paradigms like progressive ratio schedule and intermittent access. Gene expression profiles were evaluated in the striatum using whole-genome microarrays and qPCR. RESULTS: The animals drinking morphine showed addiction-related behavioral pattern when compared with control animals. The analysis of molecular changes revealed long-lasting alterations in gene expression profiles between the analyzed groups of animals. Interestingly, correlation analyses between individual gene expression levels and motivation allowed to identify genes (Epha5, Ncam) that possibly indicate predisposition to addiction-like behaviors. CONCLUSIONS: Our model represents a novel approach for investigating both behavioral and molecular mechanisms of addiction. Mice drinking morphine exhibit many of the addiction-like symptoms compared to control animals. Prolonged morphine intake resulted in adaptive processes in the brain that manifested as altered transcriptional sensitivity to opioids. FINANCIAL SUPPORT: Supported by Polish National Science Centre Grant no. 2013/08/A/NZ3/00848.