Opioid receptors in the human cerebellum

Abstract

Little is known regarding opioid receptors in the human cerebellum. The present [11C]diprenorphine PET study investigated opioid receptor binding in the human cerebellum in vivo, and showed a differential binding level in cerebellar cortex, vermis and dentate nuclei. The additional study in vitro of opioid receptors in human cerebellar cortex and rat brain corroborated the presence of opioidergic mechanisms in the human cerebellum in contrast to the rat. A differential cellular distribution pattern was detected for the three major opioid receptors investigated. For the mu-receptor, and at a lower level for the kappa-receptor, mRNA expression was mainly observed over granule cells. Binding sites were most prominent in the molecular layer. For the delta-receptor no signal was detected. The consideration of cerebellar opioidergic mechanisms and the distribution patterns of the various opioid receptors may promote the understanding of cerebellar function and of opioidergic pharmacology in the human.

Synthesis, NMR characterization and pharmacological evaluation of ligands derived from diprenorphine for central opioid receptors imaging

“…The solvent was evaporated under reduced pressure to obtain 3-acetyldiprenorphine 2 as a white crystalline solid (93.7 mg, 100%). 1 ; the other proton assignments of DPN are in agreement with previous studies. 19 13 ; the other proton assignments of DPN are in agreement with previous studies.…”

“…In order to understand more thoroughly the role and the functions of the opioid receptors and their interactions with effectors in vivo, the development of metabolically stable non-peptidic ligands with high affinity and good penetration in the central nervous system is a research area in constant development. Opioid receptors are widely distributed in mammalian systems, both in the central nervous system, 1 and at the periphery. 2 It is generally thought that stimulation of m receptors leads to analgesic effects, respiratory depression, euphoria and physical dependence, 3 whereas k receptors, when stimulated, produce analgesia; 4 receptors play a role in spinal analgesia but are involved in other biological processes such as immune response.…”

BOLD Imaging in Awake Wild-Type and Mu-Opioid Receptor Knock-Out Mice Reveals On-Target Activation Maps in Response to Oxycodone

“…This is made possible by the many reciprocal connections between the cerebellum, hypothalamus, limbic cortex, amygdala, and hippocampus (Snider and Maiti, 1976; Heath et al, 1978; Haines et al, 1984; Rogers et al, 2011) and the presence of opioid receptors in the cerebellum. The human cerebellum has both μ and κ opioid receptors but not δ (Schadrack et al, 1999). The many studies on opioid receptor localization in the CNS of rodents (Atweh and Kuhar, 1977; Goodman et al, 1980; Moskowitz and Goodman, 1984; Tempel and Zukin, 1987; Sharif and Hughes, 1989; Mansour et al, 1994a,b; 1995) are all in agreement as to the absence of μ and δ receptor in the cerebellum.…”

Methadone-Induced Toxic Brain Damage

“…Methadone is a synthetic opioid, with high affinity for the mu class of opioid receptors, which predominate in the cerebellum and limbic systems in humans [1]. Several reported cases illustrate the cerebellarpredominant toxicity of methadone and heroin overdose [2, 3].…”