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Publication : An antisense oligodeoxynucleotide to the mu opioid receptor attenuates cocaine-induced behavioral sensitization and reward in mice.

First Author  Hummel M Year  2006
Journal  Neuroscience Volume  142
Issue  2 Pages  481-91
PubMed ID  16893609 Mgi Jnum  J:113142
Mgi Id  MGI:3664670 Doi  10.1016/j.neuroscience.2006.06.013
Citation  Hummel M, et al. (2006) An antisense oligodeoxynucleotide to the mu opioid receptor attenuates cocaine-induced behavioral sensitization and reward in mice. Neuroscience 142(2):481-91
abstractText  Numerous studies support a role for the endogenous opioid system in cocaine-influenced behavior. Few of these studies, however, selectively delineate a role for the mu opioid receptor (MOR) in this regard. This investigation examined if the MOR modulates cocaine-induced behavior in mice using a 17-base antisense oligodeoxynucleotide (AS ODN) directed against the MOR coding sequence 16-32. Specifically, cocaine-induced behavioral sensitization and conditioned reward were investigated. For the sensitization study, C57BL/6J mice received eight intermittent i.c.v. infusions of saline, mismatch oligodeoxynucleotide (ODN) (20 mug/4 mul) or AS ODN (20 mug/4 mul) over 20 days. Mice also received concomitant once daily i.p. injections of saline (4 ml/kg) or cocaine (15 mg/kg) for 10 days. There was a 7-day withdrawal period, after which all mice were challenged with cocaine (15 mg/kg) to test for behavioral sensitization. For the conditioned place preference (CPP) study, mice received five i.c.v. infusions of mismatch ODN or MOR AS ODN (days 1-5). An unbiased counterbalanced conditioning procedure was used where mice were conditioned with saline (4 ml/kg, i.p.) and cocaine (15 mg/kg, i.p.) on alternate days for four sessions (days 3-6). Mice were tested on day 7 for CPP. Immediately following testing, [(3)H]DAMGO (d-Ala(2), N-Me-Phe(4), Gly-ol(5)-enkephalin) receptor binding to brain homogenates was conducted. MOR AS attenuated cocaine-induced behavioral sensitization and conditioned reward. MOR AS ODN also reduced [(3)H]DAMGO binding. Collectively, these findings implicate the MOR as playing an important neuromodulatory role in the behavioral effects of cocaine in mice.
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