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Cue‐conditioned alcohol seeking in rats following abstinence: involvement of metabotropic glutamate 5 receptors
Author(s) -
Adams CL,
Short JL,
Lawrence AJ
Publication year - 2010
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.2009.00562.x
Subject(s) - metabotropic receptor , pharmacology , antagonist , metabotropic glutamate receptor , chemistry , medicine , glutamate receptor , endocrinology , receptor
Background and purpose: The current study was designed to: (i) examine whether functional interactions occur between receptors known to regulate alcohol self‐administration; and (ii) characterize relapse to alcohol seeking following abstinence. Experimental approach: The selective cannabinoid CB 1 receptor antagonist SR141716A (0.03–1.0 mg·kg −1 i.p.) resulted in a dose‐dependent reduction in ethanol self‐administration in ethanol‐preferring Indiana‐preferring rats. SR141716A was then co‐administered with either the selective glutamate metabotropic glutamate 5 (mGlu 5 ) receptor antagonist 3‐[(2‐methyl‐1,3‐thiazol‐4‐yl)ethynyl]pyridine (MTEP) or the selective adenosine A 2A receptor antagonist SCH58261. Key results: When administered at individually sub‐threshold doses, a combination of SR141716A (0.1 mg·kg −1 ) and SCH58261 (0.5 mg·kg −1 i.p.) produced a reduction (28%) in ethanol self‐administration. Combinations of threshold doses of SR141716A (0.3 mg·kg −1 ) and SCH58261 (2.0 mg·kg −1 , i.p.) caused an essentially additive reduction (68%) in alcohol self‐administration. A combination of individually sub‐threshold doses of CB 1 and mGlu 5 receptor antagonists did not affect alcohol self‐administration; however, combined threshold doses of SR141716A (0.3 mg·kg −1 ) and MTEP (1.0 mg·kg −1 i.p.) did reduce ethanol self‐administration markedly (80%). Cue‐conditioned alcohol seeking was attenuated by pretreatment with MTEP (1.0 mg·kg −1 ) co‐administered with SR141716A (0.3 mg·kg −1 i.p.). In contrast, SCH58261 (2.0 mg·kg −1 ) co‐administered with SR141716A (0.3 mg·kg −1 i.p.) did not reduce cue‐conditioned alcohol seeking. Conclusions and implications: Adenosine A 2A and cannabinoid CB 1 receptors regulated alcohol self‐administration additively, but combined low‐dose antagonism of these receptors did not prevent cue‐conditioned alcohol seeking after abstinence. In contrast, combined low‐dose antagonism of mGlu 5 and CB 1 receptors did prevent relapse‐like alcohol seeking after abstinence, suggesting a prominent role for mGlu 5 receptors in this paradigm.