1. Cue-conditioned alcohol seeking in rats following abstinence: involvement of metabotropic glutamate 5 receptors.
- Author
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Adams, CL, Short, JL, Lawrence, AJ, Adams, C L, Short, J L, and Lawrence, A J
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ALCOHOLISM , *LABORATORY rats , *TEMPERANCE , *GLUTAMIC acid , *CELL receptors , *ADENOSINES , *DISEASE relapse , *ALCOHOLS (Chemical class) , *ANIMAL experimentation , *COMPARATIVE studies , *CONDITIONED response , *ETHANOL , *HETEROCYCLIC compounds , *RESEARCH methodology , *MEDICAL cooperation , *NEUROTRANSMITTER receptors , *PIPERIDINE , *PYRIDINE , *RATS , *RESEARCH , *SELF medication , *EVALUATION research , *PROMPTS (Psychology) , *EXCITATORY amino acid antagonists , *THERAPEUTICS - Abstract
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. [ABSTRACT FROM AUTHOR]- Published
- 2010
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