Different effects on the responses of functional pre- and postsynaptic 5-HT1A receptors by repeated treatment of rats with the 5-HT1A receptor agonist 8-OH-DPAT.
The effects of repeated treatment of rats with 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), 1.0 mg/kg, subcutaneously, twice daily for 7 days, on the stimulation of post- and presynaptic 5-HT1A receptors were examined. The postsynaptic responses, hypothermia and inhibition of the cage-leaving response, evoked by 0.05 mg/kg 8-OH-DPAT, were measured 48 hr after the final injection. Another postsynaptic response, the 5-HT syndrome (flat body posture and forepaw treading) was observed after the third injection of 8-OH-DPAT (1.0 mg/kg s.c.). One presynaptic response examined was the 8-OH-DPAT-induced decrease in the concentration of 5-hydroxyindoleacetic acid (5-HIAA), that indicates a decrease in turnover of 5-HT, due to stimulation of 5-HT receptors on the cell bodies and measured as the ratio of 5-HIAA to 5-HT in the hippocampus, hypothalamus and medulla oblongata. Another presynaptic response was the 8-OH-DPAT-induced decrease in the accumulation of 5-hydroxytryptophan (5-HTP) in the hippocampus and hypothalamus, after inhibition of L-aromatic amino acid decarboxylase by 3-hydroxybenzylhydrazine (NSD 1015), that is due to stimulation of autoreceptors on the 5-HT cell bodies. The kinetic properties of 5-HT1A receptors in the cerebral cortex and hippocampus, hippocampus alone, hypothalamus and medulla oblongata were determined with [3H]8-OH-DPAT. It was found that the postsynaptic effects were markedly attenuated after the treatment, the hypothermic effect already after a single dose.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Neuropharmacology, CNS 1, Astra Research Centre, Södertälje, Sweden.
L G
LG
Larsson
L
L
Rényi
S B
SB
Ross
B
B
Svensson
K
K
Angeby-Möller
D006916:5-Hydroxytryptophan / Q000494:pharmacology; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001831:Body Temperature / Q000187:drug effects; D010134:Fenclonine / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D007700:Kinetics; D008297:Male; D008526:Medulla Oblongata / Q000187:drug effects / Q000378:metabolism; D009281:Naphthalenes / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011985:Receptors, Serotonin / Q000187:drug effects*; D012701:Serotonin / Q000378:metabolism; D013569:Synapses / Q000187:drug effects / Q000378:metabolism*; D013764:Tetrahydronaphthalenes / Q000378:metabolism / Q000494:pharmacology*
D009281:Naphthalenes; D011985:Receptors, Serotonin; D013764:Tetrahydronaphthalenes; D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D006916:5-Hydroxytryptophan; D010134:Fenclonine