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Role of mGluR2/3 in the behavioral‐stimulant effects of cocaine in squirrel monkeys
Author(s) -
Bauzo Rayna M.,
Zhou Mi,
Kimmel Heather L.,
Howell Leonard L.
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a777
Subject(s) - metabotropic glutamate receptor 2 , metabotropic glutamate receptor , stimulant , nucleus accumbens , metabotropic receptor , squirrel monkey , agonist , pharmacology , amphetamine , neuroscience , psychology , medicine , receptor , dopamine
Group II metabotropic glutamate receptors (mGluR2 and mGluR3) may play a role in the pathology of cocaine (COC) addiction. In rodents, repeated cocaine decreases basal glutamate, as well as the amount and phosphorylation of mGluR2/3 in the nucleus accumbens. Activation of mGluR2/3 receptors also attenuates COC self‐administration and COC‐primed reinstatement in rodents and nonhuman primates. Based on these data, we hypothesized that selective activation of mGluR2/3 would decrease the behavioral stimulant effects of COC in nonhuman primates, while inhibition of mGluR2/3 would enhance these effects. Three squirrel monkeys were trained to lever‐press under a fixed‐interval schedule of stimulus termination. The mGluR2/3 agonist, LY379268, decreased baseline response rates and shifted the COC dose‐response curve leftward. Inhibition of mGluR2/3 by LY341495 did not alter baseline or cocaine‐induced changes in response rates. Thus, stimulation of mGluR2/3 increased the apparent potency of cocaine in producing behavioral‐stimulant effects, while inhibition of mGluR2/3 did not alter these effects. These data suggest that the observed reductions in cocaine self‐administration in earlier studies may have resulted from a greater sensitivity to the effects of cocaine. Supported by USPHS Grants DA12514, DA000517, DA015092, and RR00165 and by NSF Agreement No. IBN‐9876754.