Synapse
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The repeated administration of selective kappa-opioid receptor agonists prevents the locomotor activation produced by acute cocaine administration and the development of cocaine-induced behavioral sensitization. Previous studies have shown that dopamine (DA) D2 autoreceptors modulate the synthesis and release of DA in the striatum. Evidence that kappa agonist treatment downregulates DA D2 receptors in this same brain region has recently been obtained. ⋯ These results suggest that both pre- and postsynaptic striatal DA D2 receptors may be downregulated following repeated kappa-opioid receptor agonist administration. Synapse 39:343-350, 2001. Published 2001 Wiley-Liss, Inc.
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Parkinson's disease (PD) is characterized neuropathologically by degeneration of the nigrostriatal dopaminergic pathway. With natural aging there is loss of dopaminergic cells in the substantia nigra and, consequently, loss of dopamine transporters in the striatum. It has been suggested that PD is caused by an accelerated rate of cell death. ⋯ In a subgroup of patients with hemi-PD, we found a significant loss of dopamine transporters bilaterally in the caudate nucleus and putamen. This loss was more pronounced in the putamen than in the caudate nucleus and the contralateral binding was significantly lower than the ipsilateral binding. By using age-corrected data, we estimated that in our particular patient group motor signs started when the loss of [123I]FP-CIT binding ratios in the putamen was 46-64%.
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Studies suggest that acute and chronic opioids can regulate the cAMP-dependent protein kinase (PKA) signaling pathway and that changes in this pathway may be involved in opioid tolerance. In the present study, we examined the role of cAMP-PKA on mu-opioid receptor downregulation and tolerance in mice. Mice were injected intracerebroventricular (i.c.v.) and intrathecal (i.t.) once a day with an antisense oligodeoxynucleotide directed at the mRNA for the alpha catalytic subunit of mouse PKA. ⋯ The mismatch oligodeoxynucleotide had no effect on any measure. These results suggest that PKA has a limited role in opioid agonist-induced receptor downregulation. However, the partial block of tolerance for the high infusion dose of etorphine and the complete block of tolerance for morphine and the low infusion dose of etorphine suggests that PKA may play a critical role in tolerance that is "receptor-regulation-independent."
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Clinical and preclinical data indicate that the subthalamic nucleus (STN) plays a critical role in mediating the hyper- and hypoactive behavioral states associated with increases and decreases in dopamine receptor stimulation in the basal ganglia. The present study investigates effects of dopamine receptor stimulation on slow multisecond oscillations in firing rates in STN neurons. Extracellular, single-unit recordings were performed in locally anesthetized and immobilized rats which were either intact or had received unilateral 6-OHDA lesions of the medial forebrain bundle. ⋯ The possibility that these periodic oscillations in firing rate play a significant role in basal ganglia function was supported by the observation that the time of onset of apomorphine induced alterations in amplitude and periodicity of slow oscillations in STN spike trains is coincident with the onset of behavioral effects of this drug in 6-OHDA-lesioned animals. Synapse 38:38-50, 2000. Published 2000 Wiley-Liss, Inc.
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Olfactory bulbectomized (OBX) rats show a variety of behavioral and biochemical deficits that parallel human depression. We investigated the expression of glutamate receptor subtypes in cortical and subcortical brain regions following bilateral olfactory bulbectomy in adult rats. ⋯ Neither kainate nor AMPA receptors were altered in any brain region examined. The potential significance of these results is discussed in light of experimental findings supporting a role for NMDA receptors in the mechanism of action of antidepressant drugs and the pathophysiology of major depression.