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Ionotropic Glutamate Receptor Antagonists Modulate Cue‐Induced Reinstatement of Ethanol‐Seeking Behavior
Author(s) -
Bäckström Pia,
Hyytiä Petri
Publication year - 2004
Publication title -
alcoholism: clinical and experimental research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 153
eISSN - 1530-0277
pISSN - 0145-6008
DOI - 10.1097/01.alc.0000122101.13164.21
Subject(s) - nmda receptor , pharmacology , cnqx , antagonist , kainate receptor , ampa receptor , ionotropic effect , glutamate receptor , dizocilpine , naltrexone , chemistry , psychology , receptor , medicine , biochemistry
A bstract : Background: Glutamatergic neurotransmission has been implicated in drug‐environment conditioning, but little is known about the role of glutamate in alcohol seeking maintained by alcohol‐associated cues. Therefore, we examined the effects of ionotropic glutamate receptor antagonists on cue‐induced ethanol‐seeking behavior in the extinction/reinstatement model. Methods: Rats were trained to orally self‐administer ethanol (10% w/v) and a nonrewarding (80 μM) quinine solution on randomly alternating days. Ethanol and quinine availability were signaled by olfactory discriminative stimuli (S + /S − ). In addition, ethanol delivery was accompanied by a light stimulus (CS + ) and quinine delivery by an auditory stimulus (CS − ). Thereafter, rats were subjected to extinction training during which responding had no programmed consequences. Reinstatement of responding was tested under three conditions: in the presence of the S − /CS − , S + /CS + , and S + /CS + together with a small (0.2 ml) response‐contingent oral ethanol dose at the beginning of the reinstatement session (S + /CS + /priming). We examined the effects of the noncompetitive NMDA receptor antagonist MK‐801 (0, 0.05, 0.15 mg/kg intraperitoneally), the competitive NMDA antagonist CGP39551 (0, 5, 10 mg/kg intraperitoneally), the NMDA/glycine receptor antagonist L‐701,324 (0, 2, 4 mg/kg intraperitoneally), the AMPA/kainate receptor antagonist CNQX (0, 0.5, 1.5 mg/kg intraperitoneally), and the opioid receptor antagonist naltrexone (0, 0.3, 1 mg/kg subcutaneously) on ethanol seeking under the S + /CS + /priming condition. Results: Presentation of the S + /CS + stimulus condition reinstated extinguished responding, whereas presentation of the S − /CS − condition did not. Response‐contingent ethanol priming enhanced reinstatement further. Under these reinstatement conditions, L‐701,324, CNQX, and naltrexone inhibited ethanol‐seeking behavior significantly. In contrast, MK‐801 and CGP39551 failed to affect reinstated responding. Conclusions: These results show that glutamate antagonism suppresses ethanol‐seeking behavior induced by ethanol‐paired stimuli. Furthermore, the data suggest that ionotropic glutamate receptors may have differential roles in mediation of this behavior.