Tryptamine receptors: neurochemical and electrophysiological evidence for postsynaptic and functional binding sites.
[3H]Tryptamine binding characteristics and responsiveness of spontaneously active caudate nucleus neurons to intravenous application of drugs were assessed 6 weeks following unilateral application of 6-hydroxydopamine (6-OHDA, 8 micrograms) to the substantia nigra of male Wistar rats. The effects of this lesion procedure on caudatal levels of dopamine, 5-hydroxytryptamine (5-HT) and their acid metabolites, and on pargyline-induced (200 mg/kg, 2 h, s.c.) accumulation of tryptamine in the caudate nucleus were also assessed. Levels of caudatal dopamine and metabolites were reduced ipsilateral to the lesion. Concurrently there was a reduction in the extent of pargyline-induced tryptamine accumulation. Caudatal [3H]tryptamine binding was increased ipsilateral to the lesion, indicating a postsynaptic localization of this binding site. Bmax values in the caudatal samples ipsilateral to the lesion were increased by an average of 34% relative to the contralateral side. Contralateral Bmax values were equivalent to those routinely obtained in control animals. The affinity (Kd) of these binding sites for [3H]tryptamine was unchanged by the lesion procedure. The firing rate of caudate neurons was inhibited by intravenous application of tryptamine, apomorphine and 5-MeODMT. The lesion procedure did not affect these responses to 5-MeODMT. Responses to tryptamine and to apomorphine were enhanced ipsilateral to the lesion by 10- and 3-fold respectively. Haloperidol (0.5 mg/kg, i.v.) reversed apomorphine-induced inhibition of caudatal neuronal firing rate. The effects of tryptamine were not reversed by haloperidol. These data indicate a classical adaptive increase in [3H]tryptamine binding in caudate following 6-OHDA lesions.(ABSTRACT TRUNCATED AT 250 WORDS)
van Nguyen
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Neuropsychiatric Research Unit, University of Saskatchewan, Saskatoon, Canada.
Paterson
I A
IA
Juorio
A V
AV
Greenshaw
A J
AJ
Boulton
A A
AA
D000200:Action Potentials; D000818:Animals; D002421:Caudate Nucleus / Q000378:metabolism* / Q000502:physiology; D006892:Hydroxydopamines; D008297:Male; D018377:Neurotransmitter Agents / Q000378:metabolism / Q000494:pharmacology; D016627:Oxidopamine; D051381:Rats; D011919:Rats, Inbred Strains; D011985:Receptors, Serotonin / Q000378:metabolism / Q000502:physiology*; D013378:Substantia Nigra / Q000187:drug effects / Q000502:physiology*; D014363:Tryptamines / Q000378:metabolism* / Q000494:pharmacology
D006892:Hydroxydopamines; D018377:Neurotransmitter Agents; D011985:Receptors, Serotonin; D014363:Tryptamines; C030820:tryptamine; D016627:Oxidopamine