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.
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.
Authors: Matthew J Fell; Kenneth W Perry; Julie F Falcone; Bryan G Johnson; Vanessa N Barth; Karen S Rash; Virginia L Lucaites; Penny G Threlkeld; James A Monn; David L McKinzie; Gerard J Marek; Kjell A Svensson; David L Nelson Journal: J Pharmacol Exp Ther Date: 2009-09-15 Impact factor: 4.030
Authors: Daniel S Lorrain; Hervé Schaffhauser; Una C Campbell; Christopher S Baccei; Lucia D Correa; Blake Rowe; Dana E Rodriguez; Jeffery J Anderson; Mark A Varney; Anthony B Pinkerton; Jean-Michel Vernier; Linda J Bristow Journal: Neuropsychopharmacology Date: 2003-06-25 Impact factor: 7.853