O

Opioids,

N-methyl-d-aspartate receptor in tolerance and dependence, activation, 285, 286 antagonist prevention, addiction treatment, 312, 313 antagonist types and effects, 298,

299,305, 306 chronic pain treatment, 312 dependence, 303, 304 discriminative stimulus effects, 301

history of study, 296-299, 399 locomotor depression, 299, 300 operant responding, 301 5-opioids, 283 K-opioids, 283

^-opioids, 281-283, 307, 308 reversal oftolerance and dependence,

304, 306, 307 sensitization, 302, 303 side effects and therapeutic potential,

313, 314 temperature regulation, 299

neuropathic pain and tolerance mechanism interactions, 288, 289

phase II trials of antagonists, abstinence promotion, 266 dextromethorphan, 263, 265 human models, 262, 263 ibogaine, 265 memantine, 263-265 protein kinase C role, autoradiographical and immuno-

cytochemical evidence, 285 behavioral evidence, 284, 286 electrophysiological evidence,

284, 285, 310 signaling model, 308-310 spinal cord model of ^-opioid tolerance studies, 286-288 signal transduction, 308-311 nitric oxide synthase mediation ofeffects, antisense mapping of splice variants, 401-403

blockade inhibition of tolerance,

399, 400, 404 reversal of tolerance, 400, 401 therapeutic targeting, 404, 405 ^-opioids, see Morphine tolerance deficiency in 129/SvEv mice, 404 withdrawal, glutamate receptor antagonist studies, a-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor, 332, 333

metabotropic glutamate receptor,

333,334 N-methyl-d-aspartate receptor,

331, 332 therapeutic prospects, 334 locus coeruleus activity, 329-334 nucleus accumbens role, 331 spinal cord glutamate release, 331 symptoms, 329 treatment stages, 261 Oxidative stress, antioxidant defenses in brain, 202 methamphetamine neurotoxicity, hydroxy radicals, 217

peroxynitrite, 218 superoxide radicals, 203, 217 reactive oxygen and nitrogen species in brain, 201, 202

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