Altered dopamine and serotonin metabolism in the dopamine-denervated and serotonin-hyperinnervated neostriatum of adult rat after neonatal 6-hydroxydopamine

• Published in: The Journal of pharmacology and experimental therapeutics Vol. 270; no. 2; p. 713
• Main Authors: Molina-Holgado, E, Dewar, K M, Descarries, L, Reader, T A
• Format: Journal Article
• Language: English
• Published: United States 01-08-1994
• Subjects: Animals; Animals, Newborn; Carrier Proteins - metabolism; Denervation; Dopamine - metabolism; Dopamine Plasma Membrane Transport Proteins; Female; Male; Membrane Glycoproteins - metabolism; Membrane Transport Proteins; Monoamine Oxidase Inhibitors - pharmacology; Neostriatum - drug effects; Neostriatum - metabolism; Nerve Tissue Proteins; Oxidopamine - pharmacology; Rats; Rats, Sprague-Dawley; Serotonin - metabolism; Serotonin Plasma Membrane Transport Proteins
• ISSN: 0022-3565

3,4-Dihydroxyphenylalanine (L-DOPA), 5-hydroxy-l-tryptophan (5-HTP), dopamine (DA), 5-hydroxytryptamine (5-HT) and their metabolites were measured in the rostral neostriatum of adult rats neonatally lesioned with 6-hydroxydopamine (6-OHDA) after treatment with NSD-1015 (aromatic L-amino acid decarboxylase inhibitor), pargyline (monoamine oxidase inhibitor) or probenecid (blocker of acidic metabolite efflux). Binding experiments with DA and 5-HT transporter ligands allowed us to relate observed changes to the number of DA and 5-HT terminals. One and 3 months after the lesions were made, DA, 3,4-dihydroxyphenylacetic acid (DOPAC)- and homovanillic acid (HVA)-content as well as [3H]N-[1-(2-benzo(b)-thiophenyl)cyclohexyl]piperidine ([3H]BTCP) binding were lowered to 1% to 2% of control values, reflecting a permanent DA denervation. After 1 month, 5-HT content was increased by 96% and 5-hydroxyindole-3-acetic acid (5-HIAA) was increased by 50% in the presence of control levels of [3H]citalopram binding, suggesting that there was an increased amount of 5-HT per neostriatal 5-HT terminal. At 3 months, 5-HT content had increased by 205%, 5-HIAA remained increased by 50% and [3H]citalopram binding had reached 170% of control values, indicating a persistent increase in 5-HT content within an excessive number of 5-HT terminals (hyperinnervation). At both survival times, neostriatal L-DOPA accumulation after NSD-1015 was low, but ratios of L-DOPA to DA and of L-DOPA to [3H]BTCP were greatly elevated. 5-HTP accumulation was increased, but ratios of 5-HTP to 5-HT were lower than control, despite unchanged ratios of 5-HTP to [3H]citalopram.