Send to

Choose Destination
Eur J Pharmacol. 1994 Aug 11;261(1-2):171-8.

Hypersensitivity to serotonin and its agonists in serotonin-hyperinnervated neostriatum after neonatal dopamine denervation.

Author information

Centre de Recherche en Sciences Neurologiques, Faculté de Médecine, Université de Montréal, Québec, Canada.


Neonatal destruction of the nigrostriatal dopamine projection by intraventricular 6-hydroxydopamine leads to a serotonin (5-hydroxytryptamine, 5-HT) hyperinnervation of the adult neostriatum accompanied by increased radioligand binding to 5-HT1B, 5-HT1nonAB and 5-HT2 receptors. The consequences of such 5-HT receptor changes on neuronal responsiveness to 5-HT and corresponding receptor agonists were assessed with a quantitative iontophoretic approach. For comparative purposes, similar data were also obtained from rats 6-hydroxydopamine lesioned as adults, showing severe neostriatal dopamine denervation but no 5-HT hyperinnervation. In controls, 5-HT and its receptor agonists, m-chlorophenylpiperazine (mCPP; 5-HT1B/2C agonist) and dimethoxy-iodophenyl-aminopropane (DOI; 5-HT2A/2C agonist), depressed the firing rate of a majority of the unit tested. Three months after neonatal 6-hydroxydopamine lesion (5-HT-hyperinnervated tissue), inhibitory responses to all three agents were significantly increased and comparable results were obtained for 5-HT and DOI in the rostral versus caudal neostriatum. After 6-hydroxydopamine lesion in adults, neither responsiveness to 5-HT, mCPP or DOI nor the density of 5-HT1B or 5-HT2A binding were significantly different from control. Thus, the up-regulation of 5-HT1B, 5-HT2A and possibly 5-HT2C receptors accompanying the 5-HT hyperinnervation after neonatal but not after adult dopamine denervation was associated with increased responsiveness (IT50) of neostriatal neurons to iontophoresed 5-HT and its receptor agonists. Under these conditions, neostriatal 5-HT transmission might be enhanced in spite of a basal release seemingly comparable to normal (Jackson and Abercrombie, 1992, J. Neurochem. 58, 890).(ABSTRACT TRUNCATED AT 250 WORDS).

[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center