Serotonergic innervation of the rat caudate following a neonatal 6-hydroxydopamine lesion: an anatomical, biochemical and pharmacological study.

Abstract

6-Hydroxydopamine (6-OHDA) treatment of neonatal rats resulted in a dose-related loss of striatal dopamine (DA). These reductions corresponded closely with the loss of tyrosine hydroxylase-containing terminals at this brain site. Striatal serotonin (5-HT) concentration increased only after DA was maximally depleted by the highest dose of 6-OHDA. Quantitative immunohistochemistry revealed that the increased 5-HT content after neonatal 6-OHDA lesioning was due to a proliferation of 5-HT nerve terminals. The density of immunoreactive 5-HT-containing terminals appeared to increase more than did the 5-HT content. The present study examined whether 5-HT hyperinnervation was playing a role in behavioral responses induced by D1-DA agonists and antagonists in neonatally lesioned rats, because reports have suggested that these drugs may interact with 5-HT receptors. However, SCH-23390, the D1-DA antagonist (0.3 mg/kg), did not alter behavioral responses to 5-HTP and SKF-38393 (3 mg/kg), a D1-DA agonist did not produce any signs of activating 5-HT receptors in 5,7-DHT-lesioned rats. These data indicate that these compounds affecting D1-DA receptors do not have a significant effect on 5-HT function at doses which have maximal effects on D1-DA receptor function. Pretreatment with the 5-HT antagonist methysergide did not produce a change in apomorphine-induced locomotion and did not antagonize the self-mutilation or the other behaviors produced by L-DOPA or SKF-38393 in neonatally lesioned rats, suggesting that 5-HT hyperinnervation is not responsible for these drug-induced changes in neonatal 6-OHDA-lesioned rats.

• Authors: A C Towle, H E Criswell, E H Maynard, J M Lauder, T H Joh, R A Mueller, G R Breese
• Journal: Pharmacology, biochemistry, and behavior (Pharmacol Biochem Behav) Vol. 34 Issue 2 Pg. 367-74 (Oct 1989) ISSN: 0091-3057 [Print] United States
• PMID: 2576138 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Benzazepines
• Hydroxydopamines
• Serotonin
• 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine
• Oxidopamine
• Tyrosine 3-Monooxygenase
• Methysergide

Topics

• 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine (pharmacology)
• Animals
• Animals, Newborn
• Benzazepines (pharmacology)
• Caudate Nucleus (drug effects, metabolism, pathology)
• Hydroxydopamines (pharmacology)
• Methysergide (pharmacology)
• Oxidopamine
• Rats
• Rats, Inbred Strains
• Serotonin (metabolism)
• Tyrosine 3-Monooxygenase (metabolism)