Cocaine-induced suppression of renin secretion is partially mediated by serotonergic mechanisms.
Acute cocaine reduces renin secretion. To determine whether serotonergic neurons mediate this effect, male Sprague-Dawley rats received the serotonin (5-HT) neurotoxin 5,7-dihydroxytryptamine (75 micrograms/side, ICV) 2 weeks prior to cocaine injections (3.75-15 mg/kg, IP). 5-HT lesions attenuated the cocaine-induced reduction of plasma renin concentration (PRC), suggesting a partial 5-HT role. To determine which receptors mediate this response, rats were pretreated with the partial 5-HT1A agonist 8-[2-[4-(2-methoxyphenyl)-l-piperazinyl]ethyl]-8-azaspirol-[4,5]- decane-7,9-dione (BMY 7378) (1 mg/kg, SC), the 5-HT1C/5-HT2 antagonist ritanserin (0.1 mg/kg, SC), or the alpha 2/5-HT1A antagonist yohimbine (1 mg/kg, SC) prior to cocaine. None of the antagonists altered the cocaine-induced suppression of PRC, although BMY 7378 and yohimbine elevated PRC. The data suggest that cocaine's effect is partially mediated by a serotonergic mechanism, but do not support a role for 5-HT1A receptors, 5-HT2/5-HT1C receptors, or alpha 2-adrenoceptors in mediating the suppressive effect of cocaine on renin secretion.
Levy
A D
AD
Department of Pharmacology, Stritch School of Medicine, Loyola University of Chicago, Maywood, IL 60153.
Rittenhouse
P A
PA
Li
Q
Q
Kerr
J E
JE
Cabrera
T M
TM
Battaglia
G
G
Van de Kar
L D
LD
D015116:5,7-Dihydroxytryptamine / Q000494:pharmacology; D000818:Animals; D003042:Cocaine / Q000494:pharmacology*; D007276:Injections, Intraventricular; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D010879:Piperazines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012083:Renin / Q000378:metabolism*; D016713:Ritanserin / Q000494:pharmacology; D012701:Serotonin / Q000502:physiology*; D015016:Yohimbine / Q000494:pharmacology
D010879:Piperazines; D016713:Ritanserin; D015016:Yohimbine; D015116:5,7-Dihydroxytryptamine; D012701:Serotonin; D012083:Renin; D003042:Cocaine; C053428:BMY 7378