Administration of 8-hydroxy-2-(Di-n-propylamino)tetralin in raphe nuclei dorsalis and medianus reduces serotonin synthesis in the rat brain: differences in potency and regional sensitivity.
Following administration of 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT; 0.04-5.0 micrograms/0.5 microliter) in the raphe nucleus dorsalis (DR) or medianus (MR), the synthesis of serotonin (5-HT), as assessed by the accumulation of 5-hydroxytryptophan (5-HTP) after decarboxylase inhibition, was measured in various regions of the rat CNS. At all doses, 8-OH-DPAT in the DR significantly reduced 5-HTP accumulation in the striatum, nucleus accumbens, cortex, and prefrontal cortex, whereas even the highest dose had no effect in the hippocampus, hypothalamus, and spinal cord. One microgram of 8-OH-DPAT in the MR significantly reduced 5-HTP accumulation in the nucleus accumbens and prefrontal cortex, and 5 micrograms had an effect in all the areas except the striatum and spinal cord. One and 5 micrograms of 8-OH-DPAT, administered in either the DR or MR, did not significantly modify the accumulation of dihydroxyphenylalanine in the striatum and nucleus accumbens. The results confirm that DR and MR have different sensitivities to 5-HT1A receptor agonists, and that activation of 5-HT1A receptors in these nuclei produces different effects on 5-HT synthesis in different brain regions.
Invernizzi
R
R
Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.
Carli
M
M
Di Clemente
A
A
Samanin
R
R
D006916:5-Hydroxytryptophan / Q000378:metabolism; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D000818:Animals; D001921:Brain / Q000378:metabolism*; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D005625:Frontal Lobe / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism; D011903:Raphe Nuclei / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011985:Receptors, Serotonin / Q000502:physiology; D012701:Serotonin / Q000096:biosynthesis*; D013764:Tetrahydronaphthalenes / Q000008:administration & dosage / Q000494:pharmacology*
D011985:Receptors, Serotonin; D013764:Tetrahydronaphthalenes; D012701:Serotonin; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D006916:5-Hydroxytryptophan