The group II metabotropic glutamate receptor agonist LY379268 reduces toluene-induced enhancement of brain-stimulation reward and behavioral disturbances

• Published in: Psychopharmacology 2015-09, Vol.232 (17), p.3259-3268
• Main Authors: Chan, Ming-Huan, Tsai, Yi-Ling, Lee, Mei-Yi, Stoker, Astrid K., Markou, Athina, Chen, Hwei-Hsien
• Format: Article
• Language: English
• Subjects: Amino Acids - pharmacology; Animals; Behavior, Animal - drug effects; Behavioral psychology; Biomedical and Life Sciences; Biomedicine; Brain; Brain - drug effects; Brain stimulation; Bridged Bicyclo Compounds, Heterocyclic - pharmacology; Drug abuse; Electrodes, Implanted; Genetic aspects; Glutamate; Interpersonal Relations; Male; Mice; Motor Activity - drug effects; Neurosciences; Original Investigation; Pharmacology/Toxicology; Physiological aspects; Postural Balance - drug effects; Psychiatry; Receptors, Metabotropic Glutamate - agonists; Recognition (Psychology) - drug effects; Reward; Self Stimulation - drug effects; Social aspects; Solvent abuse; Toluene; Toluene - antagonists & inhibitors; Toluene - pharmacology
• ISSN: 0033-3158; 1432-2072
• DOI: 10.1007/s00213-015-3973-3

Rationale Toluene, a widely abused solvent with demonstrated addictive potential in humans, hasbeen reported to negatively modulate N-methyl-D-aspartate receptors (NMDARs) and alter glutamatergicneurotransmission. The group II metabotropic glutamate receptor (mGluR) agonist LY379268 has beenshown to regulate glutamate release transmission and NMDAR function and block toluene-induced locomotorhyperactivity. However, remaining unknown is whether group II mGluRs are involved in the toluene-induced reward-facilitating effect and other behavioral manifestations. Objectives The present study evaluated the effects of LY379268 on toluene-induced reward enhancement, motor incoordination, recognition memory impairment, and social interaction deficits. Results Our data demonstrated that LY379268 significantly reversed the toluene-induced lowering of intracranial self-stimulation (ICSS) thresholds and impairments in novel object recognition, rotarod performance, and social interaction with different potencies. Conclusions These results indicate a negative modulatory role of group II mGluRs in acute toluene-induced reward-facilitating and behavioral effects and suggest that group II mGluR agonists may have therapeutic potential for toluene addiction and the prevention of toluene intoxication caused by occupational or intentional exposure.