As noted earlier, ionotropic glutamate receptors play an important part in the development of alcohol abuse and dependence, with many of ethanol’s effects mediated by these receptors. For instance, Enoch and coworkers147 as well as Jin and coworkers148 have reported that numerous ionotropic glutamate receptor subunit expression levels are significantly altered in chronic alcoholics and cocaine addicts, relative to control samples. Nevertheless, there has been limited behavioral–pharmacology research on the involvement of ionotropic receptors in excessive ethanol intake by P rats. Pretreatment with aniracetam, a selective positive allosteric modulator of AMPA receptors, increased operant responding for ethanol and cue-induced reinstatement of operant responding for ethanol by P rats, while not altering locomotor activity or operant responding for sucrose.149 These authors confirmed the involvement of AMPA receptors by demonstrating that the AMPA receptor antagonist 6,7-dinitroquinoxaline-2,3-dione blocked aniracetam-induced increases in ethanol self-administration. Besides the P rat, the selectively bred ALKO alcohol-accepting (high ethanol-consuming rat line from Finland) has also been used to assess the role of AMPA/kainate receptors in excessive ethanol intake, with systemic administration of the antagonist CNQX significantly reducing operant
