5-Hydroxytryptamine1A but not 5-hydroxytryptamine2 receptors are enriched on neocortical pyramidal neurones destroyed by intrastriatal volkensin.
Experimental lesions followed by binding of [3H]8-hydroxy-2-(n-dipropylamino)tetralin (8-OH-DPAT) and [3H]ketanserin to cryostat sections and quantitative autoradiography were used to investigate the cellular localization of 5-hydroxytryptamine1A (5-HT1A) and 5-hydroxytryptamine2 (5-HT2) receptors in the neocortex of the rat. The lesions were produced by intrastriatal injections of either volkensin (2 and 6 ng) or ricin (10 ng): both are suicide transport agents, but only the former is retrogradely transported in the central nervous system. Only animals treated with volkensin showed cortical receptor changes and these were almost exclusively confined to the 5-HT1A site. The binding of [3H]8-OH-DPAT was significantly reduced in rats receiving 2 or 6 ng volkensin in the deeper cortical layers of areas Fr1/Fr2 of neocortex ipsilateral to the striatal lesion. Quantitative histological analysis of adjacent sections had previously revealed a significant loss of large infragranular pyramidal neurones with sparing of both interneurones and supragranular pyramidal neurones. There was no significant reduction in [3H]8-OH-DPAT binding in superficial layers. In cortical areas, Par1/Par2 [3H]8-OH-DPAT binding was significantly reduced (2 and 6 ng animals) in both superficial and deeper cortical layers, but quantitative histological analysis has not been performed. The binding of [3H] ketanserin was unaffected except for the most superficial layers of Par1/Par2, where binding was significantly reduced in only the 2 ng animals. There was no reduction in [3H]8-OH-DPAT binding after intrastriatal ricin injection, which caused as much cell loss in the striatum as 2 ng of volkensin, but did not destroy cortical pyramidal neurones.(ABSTRACT TRUNCATED AT 250 WORDS)
Francis
P T
PT
Department of Neurochemistry, Institute of Neurology, Queen Square, London, U.K.
Pangalos
M N
MN
Pearson
R C
RC
Middlemiss
D N
DN
Stratmann
G C
GC
Bowen
D M
DM
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D000818:Animals; D001345:Autoradiography; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D006023:Glycoproteins; D007650:Ketanserin / Q000378:metabolism; D008297:Male; D009699:N-Glycosyl Hydrolases; D037121:Plant Lectins; D010940:Plant Proteins / Q000633:toxicity*; D051381:Rats; D011919:Rats, Inbred Strains; D011985:Receptors, Serotonin / Q000187:drug effects* / Q000378:metabolism; D054790:Ribosome Inactivating Proteins, Type 2; D013764:Tetrahydronaphthalenes / Q000378:metabolism
D006023:Glycoproteins; D037121:Plant Lectins; D010940:Plant Proteins; D011985:Receptors, Serotonin; D054790:Ribosome Inactivating Proteins, Type 2; D013764:Tetrahydronaphthalenes; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; C049134:volkensin; D007650:Ketanserin; D009699:N-Glycosyl Hydrolases