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Activation of nociceptin/orphanin FQ‐NOP receptor system inhibits tyrosine hydroxylase phosphorylation, dopamine synthesis, and dopamine D 1 receptor signaling in rat nucleus accumbens and dorsal striatum
Author(s) -
Olianas Maria C.,
Dedoni Simona,
Boi Marianna,
Onali Pierluigi
Publication year - 2008
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2008.05629.x
Subject(s) - nucleus accumbens , nociceptin receptor , nop , chemistry , striatum , dopamine , tyrosine hydroxylase , ventral tegmental area , receptor , medicine , microbiology and biotechnology , endocrinology , biology , biochemistry , dopaminergic , opioid , opioid peptide
Nociceptin/orphanin FQ (N/OFQ) has been reported to inhibit dopamine (DA) release in basal ganglia mainly by acting on NOP receptors in substantia nigra and ventral tegmental area. We investigated whether N/OFQ could affect DA transmission by acting at either DA nerve endings or DA‐targeted post‐synaptic neurons. In synaptosomes of rat nucleus accumbens and striatum N/OFQ inhibited DA synthesis and tyrosine hydroxylase (TH) phosphorylation at Ser40 via NOP receptors coupled to inhibition of the cAMP/protein kinase A pathway. Immunofluorescence studies showed that N/OFQ preferentially inhibited phospho‐Ser40‐TH in nucleus accumbens shell and that in this subregion NOP receptors partly colocalized with either TH or DA D 1 receptor positive structures. In accumbens and striatum N/OFQ inhibited DA D 1 receptor‐stimulated cAMP formation, but failed to affect either adenosine A 2A or DA D 2 receptor regulation of cAMP. In accumbens slices, N/OFQ inhibited DA D 1 ‐induced phosphorylation of NMDA and α‐amino‐3‐hydroxy‐5‐methylisoxazole‐4‐propionate glutamate receptors, whereas in primary cultures of accumbal cells, which were found to coexpress NOP and DA D 1 receptors, N/OFQ curtailed DA D 1 receptor‐induced cAMP‐response element‐binding protein phosphorylation. Thus, in accumbens and striatum N/OFQ exerts an inhibitory constraint on DA transmission by acting on either pre‐synaptic NOP receptors inhibiting TH phosphorylation and DA synthesis or post‐synaptic NOP receptors selectively down‐regulating DA D 1 receptor signaling.