Substituted piperazine and indole compounds increase extracellular serotonin in rat diencephalon as determined by in vivo microdialysis.
In vivo microdialysis was used to examine the effects of 5-methoxy-3-(1,2,3,6-tetrahydro-4-pyridinyl)-1H-indole (RU24969) and 1-(m-trifluoromethylphenyl)piperazine (TFMPP) on extracellular 5-hydroxytryptamine (5-HT) in the diencephalon of unanesthetized rats. Both RU24969 and TFMPP are potent 5-HT autoreceptor agonists but both compounds caused a dose-dependent increase in extracellular 5-HT, when infused into the diencephalon at micromolar concentrations. The piperazine compound, TFMPP, also caused an increase in 5-HT when administered peripherally (2.5-10 mg/kg i.p.). In contrast, peripheral administration of RU24969 (2.5 mg/kg i.p.) caused a decrease in extracellular 5-HT. Since the effects of local infusion with RU24969 and TFMPP were not additive with the increase produced by the inhibitor of the uptake of 5-HT, fluoxetine, these compounds may be acting at the site of the membrane carrier. These results suggest that direct 5-HT1 agonist activity is not the only factor involved in the physiological and behavioral consequences of peripheral administration of TFMPP.
Auerbach
S B
SB
Department of Biological Sciences, Rutgers University, New Brunswick, NJ 08855-1059.
Rutter
J J
JJ
Juliano
P J
PJ
D000818:Animals; D003956:Dialysis / Q000379:methods; D004027:Diencephalon / Q000187:drug effects / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005110:Extracellular Space / Q000187:drug effects / Q000378:metabolism; D005473:Fluoxetine / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology*; D008297:Male; D010879:Piperazines / Q000494:pharmacology*; D051381:Rats; D012701:Serotonin / Q000378:metabolism*
D007211:Indoles; D010879:Piperazines; D005473:Fluoxetine; C018406:1-(3-trifluoromethylphenyl)piperazine; C025145:5-methoxy 3-(1,2,3,6-tetrahydro-4-pyridinyl)1H indole; D012701:Serotonin