Studies on the role of 5-HT1A autoreceptors and alpha 1-adrenoceptors in the inhibition of 5-HT release--I. BMY7378 and prazosin.
The present study utilized in vivo microdialysis to investigate the importance of 5-HT1A autoreceptors and alpha 1-adrenoceptors in the decreased 5-HT release obtained following administration of the mixed 5-HT1A autoreceptor partial agonist/alpha 1-adrenoceptor antagonist BMY7378, the selective 5-HT1A receptor agonist 8-OH-DPAT and the alpha 1-adrenoceptor antagonist prazosin. BMY7378 (0.25 mg/kg, s.c.), 8-OH-DPAT (0.025 mg/kg, s.c.) and prazosin (0.1-1.0 mg/kg, s.c.) all suppressed ventral hippocampal 5-HT efflux. The BMY7378- and 8-OH-DPAT-induced inhibition of 5-HT release were reversed by a 40 min pre-treatment with either (+/-)pindolol (8 mg/kg, s.c.) or WAY-100635 (0.3 mg/kg, s.c.), to block 5-HT1A autoreceptors. Neitehr of these antagonists altered the prazosin-induced (0.3 mg/kg, s.c.) 5-HT disease.


RESULTS
(i) confirm that both an alpha 1-adrenoceptor antagonist (prazosin) and 5-HT1A autoreceptor stimulants (BMY7378 and 8-OH-DPAT) may reduce cerebral 5-HT release; (ii) support that the BMY7378-induced decrease in 5-HT release results from 5-HT1A autoreceptor agonism, rather than alpha 1-adrenoceptor blockade; and (iii) argue against "physiological" antagonism (i.e. via blockade of beta-adrenoceptors, 5-HT1B receptors or some other mechanism) as an explanation for the reversal by pindolol of 5-HT1A autoreceptor agonist-induced suppression of 5-HT release. These data support the usefulness of pindolol, as well as the more specific compound WAY-100635, to block 5-HT1A autoreceptors.
Hjorth
S
S
Department of Pharmacology, University of Göteborg, Sweden.
Bengtsson
H J
HJ
Milano
S
S
Lundberg
J F
JF
Sharp
T
T
D000818:Animals; D004305:Dose-Response Relationship, Drug; D006624:Hippocampus / Q000187:drug effects*; D008297:Male; D017551:Microdialysis; D010869:Pindolol / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology*; D011224:Prazosin / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018340:Receptors, Adrenergic, alpha-1 / Q000187:drug effects* / Q000502:physiology*; D011985:Receptors, Serotonin / Q000187:drug effects* / Q000502:physiology*; D012701:Serotonin / Q000378:metabolism*; D013997:Time Factors
D010879:Piperazines; D018340:Receptors, Adrenergic, alpha-1; D011985:Receptors, Serotonin; D012701:Serotonin; D010869:Pindolol; C053428:BMY 7378; D011224:Prazosin