Dopamine–opiate interaction in the regulation of neostriatal and pallidal neuronal activity as assessed by opioid precursor peptides and glutamate decarboxylase messenger RNA expression

• Published in: Neuroscience 1999-01, Vol.92 (3), p.945-966
• Main Authors: Mavridis, M., Besson, M.J.
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Central nervous system; Central neurotransmission. Neuromudulation. Pathways and receptors; dopamine; Dopamine - physiology; Dopamine Antagonists - pharmacology; Dynorphins - genetics; Dynorphins - metabolism; Enkephalins - genetics; Enkephalins - metabolism; Fundamental and applied biological sciences. Psychology; globus pallidus; Globus Pallidus - cytology; Globus Pallidus - physiology; glutamate decarboxylase; Glutamate Decarboxylase - genetics; Haloperidol - pharmacology; Male; Naloxone - pharmacology; Narcotic Antagonists - pharmacology; neostriatum; Neostriatum - cytology; Neostriatum - physiology; Neurons - physiology; opioid peptides; Opioid Peptides - physiology; Protein Precursors - genetics; Protein Precursors - metabolism; Rats; Rats, Wistar; Receptors, Opioid, mu - metabolism; regulation; RNA, Messenger - metabolism; Vertebrates: nervous system and sense organs
• ISSN: 0306-4522; 1873-7544
• DOI: 10.1016/S0306-4522(99)00043-3

Neostriatal GABAergic neurons projecting to the globus pallidus synthesize the opioid peptide enkephalin, while those innervating the substantia nigra pars reticulata and the entopeduncular nucleus synthesize dynorphin. The differential control exerted by dopamine on the activity of these two efferent projections concerns also the biosynthesis of these opioid peptides. Using in situ hybridization histochemistry, we investigated the role of opioid co-transmission in the regulation of neostriatal and pallidal activity. The expression of the messenger RNAs encoding glutamate decarboxylase—the biosynthetic enzyme of GABA—and the precursor peptides of enkephalin (preproenkephalin) and dynorphin (preprodynorphin) were measured in rats after a sustained blockade of opioid receptors by naloxone (s.c. implanted osmotic minipump, eight days, 3 mg/kg per h), and/or a subchronic blockade of D 2 dopamine receptors by haloperidol (one week, 1.25 mg/kg s.c. twice a day). The density of μ opioid receptors in the neostriatum and globus pallidus was determined by autoradiography. Naloxone treatment resulted in a strong up-regulation of neostriatal and pallidal μ opioid receptors that was not affected by the concurrent administration of haloperidol. Haloperidol alone produced a moderate down-regulation of neostriatal and pallidal μ opioid receptors. Haloperidol strongly stimulated the expression of neostriatal preproenkephalin and preprodynorphin messenger RNAs. This effect was partially attenuated by naloxone, which alone produced moderate increases in preproenkephalin and preprodynorphin messenger RNA levels. In the neostriatum, naloxone did not affect either basal or haloperidol-stimulated glutamate decarboxylase messenger RNA expression. A strong reduction of glutamate decarboxylase messenger RNA expression was detected over pallidal neurons following either naloxone or haloperidol treatment, but concurrent administration of the two antagonists did not result in a further decrease. The amplitude of the variations of μ opioid receptor density and of preproenkephalin and preprodynorphin messenger RNA levels suggests that the regulation of neostriatal and pallidal μ opioid receptors is more susceptible to a direct opioid antagonism, while the biosynthesis of opioid peptides in the neostriatum is more dependent on the dopaminergic transmission. The down-regulation of μ opioid receptors following haloperidol represents probably an adaptive change to increased enkephalin biosy