Different serotonin receptors mediate blood pressure, heart rate, plasma catecholamine and prolactin responses to m-chlorophenylpiperazine in conscious rats.
The serotonin (5-HT) agonist, m-chlorophenylpiperazine (m-CPP), has been shown to increase blood pressure (BP), heart rate (HR), plasma catecholamine and prolactin (PRL) concentrations and to cause hypoactivity in rodents. In the present study, we used selective 5-HT and adrenergic antagonists to study the involvement of different receptor subtypes on the effects of m-CPP in conscious, freely moving rats. Hypoactivity and PRL responses were blocked by pretreatment with metergoline but not by pretreatment with other antagonists. BP increases were antagonized by ritanserin (0.1, 0.63 and 2.0 mg/kg) and ketanserin; metergoline, xylamidine or prazosin pretreatment had only partial effects on BP responses. HR increases were antagonized by yohimbine, pindolol, ketanserin and by the two higher doses of ritanserin. After pretreatment with the two higher doses of ritanserin, m-CPP decreased markedly BP and HR. These decreases were prevented by metergoline pretreatment. Norepinephrine and epinephrine responses were dose-dependently attenuated by ritanserin; naloxone pretreatment attenuated epinephrine but not norepinephrine responses. These data suggest that hypoactivity, PRL responses, and cardiodepressive effects of m-CPP are mediated by 5-HT1 receptors. It is likely that the hypoactivity and PRL responses of m-CPP are mediated by 5-HT1B receptors, and the cardiodepressive effects by 5-HT1A receptors. Increases in BP appear to be primarily mediated by stimulation of 5-HT2 receptors. Both adrenergic and serotonergic mechanisms are involved in HR responses. The catecholamine responses to m-CPP appear to be partially mediated by 5-HT1C receptors and also by nonserotonergic mechanisms.
Bagdy
G
G
Section on Clinical Neuropharmacology, National Institute of Mental Health, Bethesda, Maryland.
Szemeredi
K
K
Kanyicska
B
B
Murphy
D L
DL
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D004837:Epinephrine / Q000097:blood*; D006339:Heart Rate / Q000187:drug effects*; D007700:Kinetics; D008297:Male; D009638:Norepinephrine / Q000097:blood*; D010879:Piperazines / Q000494:pharmacology*; D011388:Prolactin / Q000097:blood* / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011985:Receptors, Serotonin / Q000187:drug effects / Q000502:physiology*; D012016:Reference Values; D012702:Serotonin Antagonists / Q000494:pharmacology*
D010879:Piperazines; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D011388:Prolactin; C015068:1-(3-chlorophenyl)piperazine; D009638:Norepinephrine; D004837:Epinephrine