Journal of neurochemistry
-
Journal of neurochemistry · Jul 2010
Dopamine D1 and D3 receptors are differentially involved in cue-elicited cocaine seeking.
Environmental cues previously associated with reinforcing drugs can play a key role in relapse to drug seeking behaviors in humans. The mesocorticolimbic dopamine system plays a critical role in cocaine-induced neurobiological changes. Dopamine D1 and D3 receptors modulate locomotor-stimulant and positive reinforcing effects of cocaine, and cue-induced reinstatement of cocaine-seeking. ⋯ Moreover, ERK, but not the c-jun N-terminal kinase and p38, is activated in wild-type and D3 receptor mutant mice but not in D1 receptor mutant mice following CPP acquisition. D3 receptor mutant mice also exhibit sustained ERK activation compared with wild-type mice following extinction training. Our results suggest that D1 and D3 receptors differentially contribute to learned association between cues and the rewarding properties of cocaine by regulating, at least in part, ERK activation in specific areas of the brain.
-
Journal of neurochemistry · Jul 2010
Metabotropic glutamate receptors (mGluRs) regulate noxious stimulus-induced glutamate release in the spinal cord dorsal horn of rats with neuropathic and inflammatory pain.
In rats with persistent pain, spinal group I metabotropic glutamate receptor (mGluR) activity has been shown to be pronociceptive, whereas spinal group II/III activity is anti-nociceptive. In brain, group I mGluR activity produces positive feedback effects on glutamate release, whereas group II/III activity produces negative feedback effects. It is unknown whether the nociceptive versus anti-nociceptive effects of spinal group I versus group II/III mGluR activity depend on differential regulation of spinal glutamate release. ⋯ In CCI rats, formalin-induced nociception and increases in spinal glutamate concentrations were significantly attenuated by pre-treatment with CPCCOEt, MPEP, APDC, or l-AP4. In CFA rats, capsaicin-induced increases in nociception and spinal glutamate concentrations were significantly attenuated by pre-treatment with CPCCOEt, MPEP, or APDC, but not l-AP4. This study demonstrates that group I antagonists and group II/III mGluR agonists attenuated the enhanced nociception and noxious stimulus-induced glutamate release in spinal cord dorsal horn of CCI and/or CFA rats in vivo, and suggests a possible mechanism for their anti-hyperalgesic effects.
-
Journal of neurochemistry · Jul 2010
Mitochondrial protection after traumatic brain injury by scavenging lipid peroxyl radicals.
Mitochondrial dysfunction after traumatic brain injury (TBI) is manifested by increased levels of oxidative damage, loss of respiratory functions and diminished ability to buffer cytosolic calcium. This study investigated the detrimental effects of lipid peroxyl radicals (LOO(*)) and lipid peroxidation (LP) in brain mitochondria after TBI by examining the protective effects of U-83836E, a potent and selective scavenger of LOO(*) radicals. Male CF1 mice were subjected to severe controlled cortical impact TBI (CCI-TBI) and treated with either vehicle or U-83836E initiated i.v. at 15 min post-injury. ⋯ Consistent with the functional effects of U-83836E being as a result of an attenuation of mitochondrial oxidative damage, the compound significantly (p < 0.001) reduced LP-generated 4-hydroxynonenal levels in both cortical homogenates and mitochondria at both 3 and 12 h post-TBI. Unexpectedly, U-83836E also reduced peroxynitrite-generated 3-nitrotyrosine in parallel with the reduction in 4-hydroxynonenal. The results demonstrate that LOO(*) radicals contribute to secondary brain mitochondrial dysfunction after TBI by propagating LP and protein nitrative damage in cellular and mitochondrial membranes.