Effects of mGlu1 receptor blockade on working memory, time estimation, and impulsivity in rats

• Published in: Psychopharmacology Vol. 196; no. 2; pp. 211 - 220
• Main Authors: Sukhotina, Irina A., Dravolina, Olga A., Novitskaya, Yulia, Zvartau, Edwin E., Danysz, Wojciech, Bespalov, Anton Y.
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer-Verlag 01.02.2008; Springer Nature B.V
• Subjects: Analysis of Variance; Animal behavior; Animal cognition; Animals; Antagonist drugs; Behavior, Animal - drug effects; Biomedical and Life Sciences; Biomedicine; Conditioning, Operant - drug effects; Discrimination (Psychology); Dose-Response Relationship, Drug; Impulsive Behavior - physiopathology; Impulsive Behavior - prevention & control; Inhibition (Psychology); Injections, Intraperitoneal; Male; Memory; Memory - drug effects; Neurosciences; Original Investigation; Pharmacology; Pharmacology/Toxicology; Psychiatry; Psychotropic drugs; Quinolines - administration & dosage; Quinolines - pharmacology; Rats; Rats, Wistar; Receptors, Metabotropic Glutamate - antagonists & inhibitors; Reinforcement Schedule; Reward; Rodents; Time Perception - drug effects; Behavioral inhibition; Impulsivity; Rat; mGluR1; Working memory; Metabotropic glutamate receptor; Time perception
• ISSN: 0033-3158; 1432-2072
• DOI: 10.1007/s00213-007-0953-2

Rationale Metabotropic glutamate 1 (mGlu1) receptor antagonists were reported to induce cognitive deficits in several animal models using aversive learning procedures. Objective The present study aimed to further characterize behavioral effects of mGlu1 receptor antagonists using appetitively motivated tasks that evaluate working memory, timing, and impulsivity functions. Materials and methods Separate groups of adult male Wistar rats were trained to perform four food-reinforced operant tasks: delayed non-matching to position (DNMTP), differential reinforcement of low rates of responding 18 s (DRL 18-s), signal duration discrimination (2-s vs 8-s bisection), and tolerance to delay of reward. Before the tests, rats were pretreated with (3-ethyl-2-methyl-quinolin-6-yl)-(4-methoxy-cyclohexyl)-methanone methanesulfonate (EMQMCM; 2.5–10 mg/kg, i.p.; JNJ16567083). Results In DNMTP task, EMQMCM produced delay-dependent increases in performance accuracy so that, at 10 mg/kg dose level, percentage of correct lever choices was enhanced at 8- and 16-s delays. In DRL task, at all three tested doses, response rates were higher, and reinforcement rates were lower than under control conditions. In signal duration discrimination tasks, EMQMCM did not have any specific effects on temporal control. In tolerance to delay of reward, EMQMCM (5 and 10 mg/kg) facilitated choice of the lever associated with large reward at longer delay levels. Conclusions Blockade of mGlu1 receptors improves working memory and reduces impulsive choice at the doses that have no effects on time perception but appear to facilitate impulsive action.