High and low affinity 5-HT2 and 5-HT1C binding sites: responses to neonatal 5,7-DHT lesions in rat brain
Pranzatelli, M.R.; Gregory, C.M.
Cytobios 75(302-303): 197-209
1993
ISSN/ISBN: 0011-4529 PMID: 8243108 Document Number: 406579
5-HT receptor denervation supersensitivity has been proposed to explain behavioural supersensitivity to L-5-HTP in rats with 5,7-dihydroxytryptamine (5,7-DHT) lesions. No upregulation of 5-HT-2 binding sites was found despite supersensitivity to putative 5-HT-2,1C drugs. To test the hypothesis that the 5-HT-1C properties of these drugs are involved instead, dose-response and time-course studies of 5-HT-1C and 5-HT-2 receptors were performed using several different radioligands in rat brain after making neonatal 5,7-DHT lesions by intraperitoneal injection. 5-HT-1C sites labelled with (3H)-mesulergine showed a distinct regional distribution: brainstem gt diencephalon gt cortex gt hippocampus gt cerebellum, constituting 65, 70, 31, 70, and 73% of total sites labelled by (3H)-mesulergine in the absence of 20 nM spiperone to block 5-HT-2 sites, respectively. 5,7-DHT lesions did not significantly alter B-MAX, K-D, or n-H of (3H)-mesulergine-labelled 5-HT-1C sites in cortex or other regions but did not reduce the density of cortical (3H)-paroxetine sites (-55%). Cortical 5-HT-1C sites labelled by (3H)-5-HT or (3H)-mianserin, and cortical 5-HT-2 sites labelled by (3H)-DOB or (3H)-ketanserin, were also unaffected. These data suggest that although denervation supersensitivity of 5-HT-1C or 5-HT-2 receptors may occur at the level of the receptor transducer-effector, there is no evidence it occurs at the receptor recognition site.