| Abstract No.: | B-B2056 |
| Country: | Canada |
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| Title: | DIFFERENTIAL EXPRESSION OF NUCLEAR RECEPTORS NUR77 AND NOR-1 IN FISCHER 344 AND LEWIS RATS TREATED WITH A NEUROTENSIN ANALOG |
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| Authors/Affiliations: | 2 Jérôme Maheux*; 1 Faïza Benaliouad; 2 Marc-Olivier Ratté; 1 Pierre-Paul Rompré; 2 Daniel Lévesque;
1 University of Montreal, Centre de Recherche Fernand Seguin, QC, Canada; 2 University of Montreal, Faculty of Pharmacy, QC, Canada
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| Content: | Introduction: Fischer (F344) and Lewis (LEW) are two inbred rat strains that have been used in drugs of abuse studies because they display very distinct differences in appetitive and consuming responses to numerous drugs such as psychostimulants, opioids, ethanol and nicotine. Neurotensin is a neuropeptide that modulates limbic dopamine neurotransmission and can produce psychostimulant- or neuroleptic-like effects depending on its site of action. Intracerebroventricular (ICV) injections of an active neurotensin analogue, [D-Tyr11]neurotensin, induce differential behavioral response in LEW compared to F344 rats, a response that is reminiscent of the effect of psychostimulants such as amphetamine. Recently, orphan transcription factors of the nuclear receptor family Nur77 and Nor-1 have been shown to be closely associated with dopamine neurotransmission. Objective: Therefore, in an attempt to identify neurochemical correlates that might explain the difference in the phenotype observed in F344 and LEW rats, we evaluated Nur77 and Nor-1 mRNA levels in these two strains of rats microinjected with [D-Tyr11]neurotensin. Methods: Groups of F344 and LEW rats were microinjected ICV with [D-Tyr11]neurotensin (18 nmol/10 ul) or saline and sacrificed under CO2 anesthesia after one hour. Behavioral measurements (Ambulatory, non-ambulatory and vertical activity) were assessed in an Opto-Variex Auto Track System immediately after the injection. Nur77 and Nor-1 mRNA levels were detected by in situ hybridization with specific radiolabeled ribonucleic probes.
Results: As previously reported, F344 and LEW rats displayed distinct locomotor responses following ICV injections of [D-Tyr11]neurotensin. The neurotensin analogue strongly increased ambulatory activity in F344 rats, whereas LEW rats showed only a marginal locomotor response. In situ hybridization revealed a differential basal expression of the Nur77 transcript between strains of rats in the nucleus accumbens, medial prefrontal and cingulate cortices. Furthermore, [D-Tyr11]neurotensin induced contradictory changes in Nur77 mRNA levels in both strains. [D-Tyr11]neurotensin tends to reduce Nur77 mRNA levels in F344, whereas, it strongly increases Nur77 mRNA levels in LEW rats. On the other hand, no significant differences in basal Nor-1 mRNA levels have been noticed between strains, while [D-Tyr11]neurotensin induced Nor-1 transcript mainly in the nucleus accumbens of F344 rats. Conclusion: These results show that activation of central neurotensin receptors produces distinct patterns of modulation of Nur77 and Nor-1 mRNA levels. These differential patterns correlate with distinct locomotor responses observed between F344 and LEW rats. These results suggest that transcription factors of the Nur family might contribute to distinct drug-induced locomotor responses observed in these rat strains. JM holds a studentship from the Fonds de la Recherche en Santé du Québec (FRSQ). |
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