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.
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