RATIONALE AND OBJECTIVES: We previously found that the inhibition of median raphe nucleus (MRN) 5-HT transmission by local injections of a 5-HT1A agonist 8-OH-DPAT or corticotrophin-releasing factor (CRF) mimic the effect of foot shock stress to reinstate alcohol seeking. In this study, we further explored the role of the MRN by examining the effect of inhibition of MRN neurons, by injecting the GABA-A receptor agonist muscimol, on the reinstatement of alcohol seeking. MATERIALS AND METHODS: Male rats were trained to lever press for 12% alcohol. Cannulae were implanted aimed at the MRN; some rats were also given intra-MRN injections of 5,7-DHT to destroy ascending 5-HT neurons. After retraining, alcohol responding was extinguished for 14 days. Subsequently, we tested the effect of muscimol injections into the MRN (0, 12.5, 25, 50 ng) on reinstatement. We also tested the effect of MRN muscimol injections on a measure of reward, conditioned place preference (CPP) and performance in the five-choice serial reaction time task (5-CSRTT), which tests a variety of psychological processes including sustained attention and impulsivity. RESULTS: MRN muscimol injections strongly reinstated alcohol seeking and this effect was not reversed by the depletion of 5-HT with 5,7-DHT. MRN muscimol injections did not induce a CPP, but did significantly impair multiple aspects of performance on the 5-CSRTT, including a marked increase in premature, or impulsive, responding. CONCLUSIONS: Together with our previous findings, these results suggest that the inhibition of MRN projection neurons provokes alcohol seeking. Results from the 5-CSRTT suggest that increased impulsivity may contribute to these effects.
RATIONALE AND OBJECTIVES: We previously found that the inhibition of median raphe nucleus (MRN) 5-HT transmission by local injections of a 5-HT1A agonist 8-OH-DPAT or corticotrophin-releasing factor (CRF) mimic the effect of foot shock stress to reinstate alcohol seeking. In this study, we further explored the role of the MRN by examining the effect of inhibition of MRN neurons, by injecting the GABA-A receptor agonist muscimol, on the reinstatement of alcohol seeking. MATERIALS AND METHODS: Male rats were trained to lever press for 12% alcohol. Cannulae were implanted aimed at the MRN; some rats were also given intra-MRN injections of 5,7-DHT to destroy ascending 5-HT neurons. After retraining, alcohol responding was extinguished for 14 days. Subsequently, we tested the effect of muscimol injections into the MRN (0, 12.5, 25, 50 ng) on reinstatement. We also tested the effect of MRN muscimol injections on a measure of reward, conditioned place preference (CPP) and performance in the five-choice serial reaction time task (5-CSRTT), which tests a variety of psychological processes including sustained attention and impulsivity. RESULTS: MRN muscimol injections strongly reinstated alcohol seeking and this effect was not reversed by the depletion of 5-HT with 5,7-DHT. MRN muscimol injections did not induce a CPP, but did significantly impair multiple aspects of performance on the 5-CSRTT, including a marked increase in premature, or impulsive, responding. CONCLUSIONS: Together with our previous findings, these results suggest that the inhibition of MRN projection neurons provokes alcohol seeking. Results from the 5-CSRTT suggest that increased impulsivity may contribute to these effects.
Authors: Andrzej Jakubczyk; Małgorzata Wrzosek; Jacek Lukaszkiewicz; Joanna Sadowska-Mazuryk; Halina Matsumoto; Elżbieta Sliwerska; Jennifer Glass; Margit Burmeister; Kirk J Brower; Marcin Wojnar Journal: J Psychiatr Res Date: 2011-09-17 Impact factor: 4.791
Authors: Jennifer L Perry; Jane E Joseph; Yang Jiang; Rick S Zimmerman; Thomas H Kelly; Mahesh Darna; Peter Huettl; Linda P Dwoskin; Michael T Bardo Journal: Brain Res Rev Date: 2010-09-15
Authors: Anh Dzung Lê; Douglas Funk; Stephen Harding; Walter Juzytsch; Paul J Fletcher Journal: Psychopharmacology (Berl) Date: 2009-02-20 Impact factor: 4.530