ergoline and xylamidine

Previously we reported that 5 min after intracerebroventricular (i.c.v.) injection, serotonin (5-HT, 2.5 micrograms) produced increases in blood pressure and decreases in heart rate in conscious rats that were blocked by LY 53857 (a selective 5-HT2/1C antagonist) and were sensitive to vasopressin antagonism. The present studies were performed to determine if this dose of 5-HT acts similarly to increase plasma vasopressin levels. In addition, the vasopressin responses were compared to prolactin, corticosterone, and plasma renin activity, three other neuroendocrine systems regulated in part by 5-HT. The administration of 5-HT (2.5 micrograms i.c.v.) produced a rapid (maximum response in less than 5 min) and brief (return to baseline by 15 min) increase in plasma vasopressin levels. The response was eliminated by the centrally acting 5-HT2/1C antagonist LY 53857 (100 micrograms/kg i.v.), but only attenuated by xylamidine (100 micrograms/kg i.v.), a 5-HT2/1C antagonist that reportedly does not cross the blood-brain barrier. 5-HT also increased plasma prolactin and corticosterone levels, but neither LY 53857 nor xylamidine altered these responses. In rats rendered chronically baroreceptor deficient by sinoaortic deafferentation, the vasopressin response to 5-HT was reduced, whereas the prolactin response was normal. 5-HT did not increase plasma renin activity in intact or baroreceptor-deficient rats, in contrast to the other neuroendocrine systems studied. Thus, the data demonstrate that vasopressin levels are elevated briefly following 5-HT i.c.v., consistent with the pharmacologic profile of the early cardiovascular response.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Amidines; Animals; Corticosterone; Denervation; Ergolines; Injections, Intravenous; Kinetics; Male; Pressoreceptors; Prolactin; Rats; Rats, Sprague-Dawley; Renin; Serotonin; Serotonin Antagonists; Sinus of Valsalva; Vasopressins

The purpose of this experiment was to examine the effects of administration of serotonergic (5-HT) agonist and antagonist drugs on run-time to exhaustion (RUN-EXH) in male and female rats. RUN-EXH was reduced (p < 0.05) in a dose related manner by increasing dosages of quipazine dimaleate (QD: general 5-HT agonist) (0-5 mg.kg-1 i.p.) administered immediately prior to exercise (treadmill running at 20 m.min-1 and 5% grade). Conversely, RUN-EXH was increased (p < 0.05) by the greatest dosage of LY 53,857 (LY: 5-HT1C and 5-HT2 antagonist) (1.5 mg.kg-1 i.p.). Drug effects were similar in male and female rats. The negative effects of QD administration on RUN-EXH were not attenuated by administration of the peripherally restricted antagonist, xylamidine tosylate (up to 200 ug.kg-1 i.p.). The results of this investigation indicated that fatigue during prolonged exercise can be influenced by direct pharmacological administration of a serotonergic agonist and antagonist and that the mechanisms underlying these effects are likely to be central (brain) in nature.

Topics: Amidines; Animals; Dose-Response Relationship, Drug; Ergolines; Female; Injections, Intraperitoneal; Male; Physical Endurance; Placebos; Quipazine; Rats; Rats, Wistar; Running; Serotonin Antagonists; Time Factors

Serotonin (5-HT) and 5-HT agonists act on multiple 5-HT receptor subtypes to increase corticosterone secretion. The present experiments describe the effects of a highly selective 5-HT2 receptor agonist DOI [(+-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane HCl] on plasma corticosterone in conscious, unrestrained, male rats with indwelling arterial and venous catheters. DOI (500 micrograms/kg, i.v.) increased plasma corticosterone levels 6- to 7-fold from 15 to 60 min. Pretreatment with the central 5-HT2 antagonist LY 53857 (100 micrograms/kg, i.v.) blocked the effect of DOI on corticosterone secretion at all times. The peripheral 5-HT2 antagonist xylamidine (100 micrograms/kg, i.v.) attenuated the corticosterone response elicited 15 min after DOI but did not alter the 60-min response. In contrast, dexamethasone pretreatment (350 micrograms/kg, s.c.) attenuated the corticosterone response to DOI at 15 min, but abolished the response at 60 min. The increase in corticosterone levels elicited 5 min after the nonselective 5-HT agonist quipazine (3 mg/kg, i.v.) was also reduced by xylamidine. These data suggest that 5-HT2 receptor agonists increase corticosterone secretion initially, in part, through a direct adrenal mechanism not entirely dependent on adrenocorticotropin, and at later times via a central, dexamethasone-suppressible mechanism. This raises the possibility that endogenous 5-HT in the adrenal medulla may act as a local paracrine to participate in the regulation of corticosterone secretion from the adrenal cortex.

Topics: Amidines; Amphetamines; Animals; Corticosterone; Dexamethasone; Ergolines; Male; Quipazine; Rats; Rats, Inbred Strains; Receptors, Serotonin; Serotonin Antagonists

Previous literature suggests that the anorexic action of peripherally administered serotonin (5-HT) is mediated by 5-HT2 receptors. This study, therefore, examined the effect of DOI, a non-indole 5-HT2 agonist, on deprivation-induced feeding. Rats were first adapted to a schedule in which a milk diet was presented for 6 h daily. Intraperitoneal (IP) administration of DOI (1.0-11.2 mumol/kg) inhibited feeding in a dose-related fashion (ID50 = 2.6 mumol/kg). One hour pretreatment with 6.0 mumol/kg of the 5-HT2 antagonists ketanserin and LY53857 completely reversed the anorexic action of an equimolar dose of DOI. Neither ketanserin nor LY53857, alone, altered baseline feeding. Further testing demonstrated the antagonistic effect of LY53857 (0.047-6.0 mumol/kg, IP) to be dose related, with an ID50 of 0.14 mumol/kg. Ten minute pretreatment with 1-(1-naphthyl)-piperazine (1-NP; 2.0 or 4.0 mumol/kg), a mixed-acting agent with 5HT2 blocking actions, also attenuated the anorexic effect of 6.0 mumol/kg DOI. Unlike ketanserin and LY53857, however, 1-NP did reduce food intake by itself. By contrast with ketanserin, LY53857 and 1-NP, the peripherally-acting 5-HT2 antagonist xylamidine failed to alter the anorexic effect of DOI. Taken together, these results suggest that central 5-HT2 receptors are important in the control of ingestive behavior.

Topics: Amidines; Amphetamines; Animals; Appetite Depressants; Diet; Eating; Ergolines; Ketanserin; Male; Rats; Rats, Inbred Strains; Serotonin Antagonists