title: The kappa-opioid receptor agonist U-69593 prevents cocaine-induced phosphorylation of DARPP-32 at Thr(34) in the rat brain.
abstract: DARPP-32 (dopamine- and cAMP-regulated phosphoprotein) is a potent endogenous inhibitor of protein phosphatase-1, which plays an important role in dopaminergic transmission. A large body of evidence supports the key role of DARPP-32-dependent signalling in mediating the actions of multiple drugs of abuse, including cocaine, which, when acutely administered, increases the Thr(34) phosphorylation of DARPP-32 in the striatal and cortical areas. In this study, we have examined the contribution of the kappa opioid system to the regulation of DARPP-32 phosphorylation at Thr(34), following acute cocaine administration, in selected rat brain areas. Results showed that a single injection of cocaine induces a significant increase in DARPP-32 phosphorylation at Thr(34) in the hippocampus, caudate putamen and prefrontal cortex. In addition, pretreatment with the kappa opioid receptor agonist U-69593 prevented cocaine effects in all the investigated areas. These data could be considered consistent with the ability of kappa opioid agonists to attenuate many behavioural and neurochemical effects of cocaine.
authors.affiliation: Department of Pharmacology, University of Bologna, Irnerio 48, Bologna 40126, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: D'Addario
authors.forename: Manuela
authors.initials: M
authors.lastname: Di Benedetto
authors.forename: Sanzio
authors.initials: S
authors.lastname: Candeletti
authors.forename: Patrizia
authors.initials: P
authors.lastname: Romualdi
mesh_terms: D000700:Analgesics / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D044482:Benzeneacetamides / Q000008:administration & dosage / Q000494:pharmacology*; D015153:Blotting, Western; D001923:Brain Chemistry / Q000187:drug effects*; D002421:Caudate Nucleus / Q000187:drug effects / Q000502:physiology; D003042:Cocaine / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D051937:Dopamine and cAMP-Regulated Phosphoprotein 32 / Q000378:metabolism*; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology; D007267:Injections; D008297:Male; D010766:Phosphorylation / Q000187:drug effects; D017397:Prefrontal Cortex / Q000187:drug effects / Q000502:physiology; D011699:Putamen / Q000187:drug effects / Q000502:physiology; D011759:Pyrrolidines / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017473:Receptors, Opioid, kappa / Q000819:agonists*; D013912:Threonine / Q000378:metabolism*
chemical_list: D000700:Analgesics; D044482:Benzeneacetamides; D051937:Dopamine and cAMP-Regulated Phosphoprotein 32; C497930:Ppp1r1b protein, rat; D011759:Pyrrolidines; D017473:Receptors, Opioid, kappa; D013912:Threonine; D003042:Cocaine; C045444:U 69593