Differential reductions in alcohol consumption and cue-induced alcohol-seeking behavior following mGlu5 receptor inhibition in the prelimbic vs. infralimbic subregions of the rat prefrontal cortex.
Jonna M Leyrer-Jackson, Peter R Kufahl, M Foster Olive
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引用次数: 0
Abstract
Glutamatergic signaling is one of the primary targets of actions of alcohol in the brain, and dysregulated excitatory transmission in the prefrontal cortex (PFC) may contribute problematic drinking and relapse. A prominent component of glutamate signaling is the type 5 metabotropic glutamate (mGlu5) receptor. However, little is known about the role of this receptor type in subregions of the PFC that regulate either alcohol intake or alcohol-seeking behavior. Here we examined the effects of microinfusions of the selective mGlu5 inhibitor 3-((2-methyl-1,3-thiazol-4-yl)ethynyl)pyridine (MTEP) into either the prelimbic (PL) or infralimbic (IL) regions of the PFC on alcohol intake or cue-evoked reinstatement of alcohol-seeking behavior. Adult male Wistar rats were trained to self-administer 10 % alcohol in the presence of compound discriminative stimuli (SD) signaling alcohol availability (S+) or non-availability (S-). In one group of animals, effects of locally administered MTEP (0, 0.5 or 1 μg/μl) into either the PL or IL on active alcohol intake were examined. MTEP was without effect on alcohol self-administration when infused into the PL, but decreased alcohol intake at both doses tested when infused into the IL. In separate groups of animals, we examined effects of locally administered MTEP (0, 0.5 or 1 μg/μl) into either the PL or IL on reinstatement of alcohol seeking elicited by alcohol predictive stimuli (S+). When infused into the PL, MTEP attenuated cue-induced reinstatement only at the higher dose tested (1 μg/μl), but when infused into the IL, MTEP reduced cue-induced reinstatement at both doses tested (0.5 μg/μl and 1 μg/μl). Together, these results suggest a largely preferential role for mGlu5 signaling in the IL vs. PL in regulating both alcohol self-administration behavior and cue-elicited alcohol seeking. Neuromodulatory approaches aimed at reducing mGlu5 signaling in the IL may therefore be of potential therapeutic value in problematic alcohol use.
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Pharmacology Biochemistry & Behavior publishes original reports in the areas of pharmacology and biochemistry in which the primary emphasis and theoretical context are behavioral. Contributions may involve clinical, preclinical, or basic research. Purely biochemical or toxicology studies will not be published. Papers describing the behavioral effects of novel drugs in models of psychiatric, neurological and cognitive disorders, and central pain must include a positive control unless the paper is on a disease where such a drug is not available yet. Papers focusing on physiological processes (e.g., peripheral pain mechanisms, body temperature regulation, seizure activity) are not accepted as we would like to retain the focus of Pharmacology Biochemistry & Behavior on behavior and its interaction with the biochemistry and neurochemistry of the central nervous system. Papers describing the effects of plant materials are generally not considered, unless the active ingredients are studied, the extraction method is well described, the doses tested are known, and clear and definite experimental evidence on the mechanism of action of the active ingredients is provided.
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