Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P08908 (5-HT1A)
 5,574 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The hyperphagic effects of two selective 5-HT1A agonists (8-OHDPAT and buspirone) in a free feeding paradigm and the locomotor suppressant effect of the serotonin agonist, m-chlorophenylpiperazine (m-CPP) were compared in three different rat strains: Wistar, Sprague-Dawley (SD), and Fawn-Hooded (FH) rats. Administration of various doses of 8-OHDPAT and buspirone produced significant increases in two-hour food intake only in Wistar and SD strains and not in the FH strain. Similarly, various doses of m-CPP produced significant decreases in locomotor activity only in Wistar and SD strains and not in the FH strain. Isolated FH animals gained significantly less body weight relative to both Wistar and SD animals. These findings demonstrate attenuated feeding and behavioral responses to serotonergic agonists in the FH strain relative to both Wistar and SD strains.
 ...
PMID:A comparison of feeding and locomotion responses to serotonin agonists in three rat strains. 297 92

Fenfluramine, m-chlorophenylpiperazine (m-CPP), 1-phenylpiperazine, and the buspirone metabolite, 1-(2-pyrimidyl)piperazine given intravenously to adult rhesus monkeys regularly elicited penile erections. In contrast, serotonin (5-HT) agonists with 5-HT1A site specificity (8-OH-DPAT, buspirone) as well as trazodone, ritanserin, and metergoline were no different from saline in producing penile erections. Fenfluramine's effects were blocked by the 5-HT2 antagonists, ritanserin and metergoline, while m-CPP's effects were not blocked by the peripheral 5-HT antagonist, xylamidine, indicating that tumescence can be elicited by serotonergic agents which act at non-5-HT1A sites in the central nervous system.
 ...
PMID:Effects of fenfluramine, m-chlorophenylpiperazine, and other serotonin-related agonists and antagonists on penile erections in nonhuman primates. 317 81

Administration of various doses of DOI (a 5-HT2A/5-HT2C agonist) produced hyperthermia that was significantly less in the FH rat strain relative to the Wistar rat strain. Similarly, administration of various doses of ipsapirone (a 5-HT1A agonist) produced hypothermia that was significantly less in the FH rat strain relative to the Wistar rat strain. Furthermore, m-CPP (a 5-HT agonist)-induced increases in growth hormone levels were also significantly less in the FH rat strain relative to the Wistar rat strain. There was no significant difference in the levels of either 5-HT or 5-HIAA between the two rat strains in the frontal cortex, hippocampus, hypothalamus, and striatum. In the brain stem, however, both 5-HT and 5-HIAA levels were significantly lower in the FH rat strain relative to the Wistar rat strain. On the other hand, 5-HT turnover rate was significantly higher in the hypothalamus and striatum and significantly lower in the hippocampus in the FH rat strain relative to the Wistar rat strain. These findings provide further evidence for altered serotonergic function in the FH rat strain and, in addition, suggest that the FH rat strain may prove to be a useful genetic model for some neuropsychiatric disorders with possible abnormalities in serotonergic function such as depression, obsessive-compulsive disorder, and the eating disorders.
 ...
PMID:Functional and biochemical evidence for altered serotonergic function in the fawn-hooded rat strain. 753 10

Variations in serotonin neurotransmission influence alcohol consumption (AC). Levels of 5-HT and metabolites are low in some brain regions of alcohol preferring rats and in CSF of alcoholics. Pharmacological treatments which enhance serotonergic neurotransmission (uptake inhibitors, releasers, agonists) consistently reduce AC in rats. Serotonin uptake inhibitors (SUI; e.g., citalopram, fluoxetine) have been studied extensively in humans. In several double-blind randomized, placebo-controlled clinical trials, SUI have consistently decreased AC by averages of 15% to 20% in nondepressed mildly/moderately dependent alcoholics who received no other treatment. Effects were dose-dependent and not related to side effects (few and mild) or changes in anxiety or depression (not observed). SUI also decreased desire to drink and liking for alcohol, thus suggesting a mechanism for effects. Other drugs acting on the 5-HT system have been tested in humans, but results are difficult to interpret. For example, buspirone, a 5-HT1A receptor partial agonist, reduced anxiety and alcohol craving, but not AC; a 5-HT partial agonist, m-CPP, increased alcohol craving in abstinent alcoholics; modest reductions in AC were observed with a 5-HT3 antagonist, ondansetron (0.5 mg/day, but not 4 mg/day). The therapeutic potentials of these medications are being studied. For example, SUI effects on AC were enhanced by a brief psychosocial intervention. Since SUI decrease urge to drink, they may be suitable pharmacological adjuncts in relapse prevention strategies. SUI and other serotonin-altering medications are promising new neuropharmacological treatments for reducing AC.
 ...
PMID:Clinical pharmacology of serotonin-altering medications for decreasing alcohol consumption. 774 4

The effects of various 5-HT receptor subtype-selective antagonists were studied on phenylisopropylamine hallucinogen 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI)-induced hyperthermia in Wistar rats, in an attempt to characterize the 5-HT receptor subtype mediating DOI-induced hyperthermia. Intraperitoneal administration of DOI to rats produced hyperthermia with a peak effect at 60 min. Pretreatment with propranolol (beta-adrenoceptor antagonist that also has binding affinity for 5-HT1A, 5-HT1B and 5-HT2C sites), MDL-72222 or ondansetron (5-HT3 antagonists) did not attenuate DOI-induced hyperthermia. In contrast, pretreatment with metergoline (5-HT1/5-HT2 antagonist), ketanserin, LY53857, mesulergine, mianserin and ritanserin (5-HT2C/5-HT2A antagonists), as well as spiperone (5-HT1A/5-HT2A/D2 antagonist), significantly attenuated DOI-induced hyperthermia. Furthermore, daily administration of DOI (2.5 mg/kg per day) for 17 days did not produce either tolerance to its hyperthermic effect or modify m-CPP-induced hyperthermia in rats. These findings suggest that DOI-induced hyperthermia in rats is mediated by stimulation of 5-HT2A receptors.
 ...
PMID:Evidence that 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI)-induced hyperthermia in rats is mediated by stimulation of 5-HT2A receptors. 775 67

Although numerous studies in rats have demonstrated an influence of serotonin (5-HT) on male copulation, no studies have yet to demonstrate whether such a relationship exists in primate species. The present study sought to characterize 5-HT influences on male copulatory behavior of rhesus monkeys by using three different 5-HT agonists: a full 5-HT1A agonist, 8-hydroxy-2-(din-propylamino) tetralin (8-OH-DPAT); a partial 5-HT1A agonist, ipsapirone; and a 5-HT 1C/ID agonist, m-chlorophenylpiperazine (m-CPP). 8-OH-DPAT had a biphasic effect upon ejaculation latency, with low doses (5-10 micrograms/kg) producing a shortening of ejaculation latency (time from initiation of copulation to ejaculation), and the highest dose (100 micrograms/kg) producing a lengthening of ejaculation latency. Intromission frequency (number of intromissions preceding ejaculation) was affected only at 10 micrograms/kg 8-OH-DPAT with monkeys requiring fewer intromissions to ejaculation at this dose. Ipsapirone administration led to a shortening of ejaculation latency at all doses tested (50-800 micrograms/kg), and a reduction in intromission frequency at 200-800 micrograms/kg ipsapirone. Administration of the 5-HT 1C/1D agonist, m-CPP, resulted in an increase in ejaculation latency at 200-400 micrograms/kg m-CPP and mount latency at 400 micrograms/kg m-CPP, but did not affect intromission frequency. In summary, stimulation of 5-HT1A receptors lowered the ejaculatory threshold of the monkeys, while stimulation of 5-HT 1C/1D receptors interfered with copulatory behavior and raised the ejaculatory threshold.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Serotonergic influences on male sexual behavior of rhesus monkeys: effects of serotonin agonists. 787 Sep 33

Effects of the non-selective 5-hydroxytryptamine (5-HT) receptor agonist m-chlorophenylpiperazine (m-CPP) on the nociceptive responsiveness in a hot plate and tail flick tests were examined in mice. Intraperitoneal administration of m-CPP (1-10 mg/kg) produced a dose-dependent antinociception in both those tests; the effect of m-CPP in the hot plate test was stronger. The antinociceptive effect of m-CPP in either test was abolished by pretreatment with mesulergine (2 mg/kg), ritanserin (1-2 mg/kg), 5-HT2A/5-HT2C receptor antagonists, and metergoline (0.5-2 mg/kg), a non-selective 5-HT receptor antagonist. On the other hand, spiperone (0.25-0.5 mg/kg), a dopamine, 5-HT1A and 5-HT2A receptor antagonist; pindolol (4-8 mg/kg), a beta-adrenoceptor, 5-HT1A and 5-HT1B receptor antagonist and zacopride (0.1-1 mg/kg) a 5-HT3 receptor antagonist, did not affect the analgesia induced by m-CPP. Neither of the drugs used as putative receptor antagonists changed the nociceptive responsiveness in mice. The obtained results suggest that the analgesia induced by m-CPP is mediated by 5-HT2C receptors.
 ...
PMID:Involvement of 5-HT2C receptors in the m-CPP-induced antinociception in mice. 789 29

The serotonin (5-HT) is implicated in many centrally-regulated functions and has shown to be involved in affective disorders, such as depression and anxiety disorders. Recent progress in pharmacology and molecular neurobiology have confirmed the concept of the heterogeneity of 5-HT receptors and permitted reformulation of new hypothesis concerning antidepressant mechanisms of action, in particular those concerning serotoninergic receptors. Up to date, among the 5-HT defined sites, only 13 have been cloned, and several subfamilies have been described. Particularly, the 5-HT1 family containing receptors: 5-HT1A, 5-HT1B/1D, 5-HT1E and 5-HT1F. The 5-HT2 family includes receptors that stimulate phospholipase C: 5-HT2A (previously termed 5-HT2), 5-HT2B and 5-HT2C (previously termed 5-HT1C). Concerning 5-HT2 family, it is possible that some 5-HT binding drugs properties initially attributed to 5-HT2A receptors, might well be mediated by 5-HT2C receptors. Recently, medifoxamine (Cledial) activities on 5-HT systems have been shown. In particular, these activities are related on 5-HT2C and/or 5-HT2A binding sites. Results indicate that, in vitro, medifoxamine affinities (Ki) are near to 1 microM, for both 5-HT2C and 5-HT2A sites (ratio = 1.42). On the other hand, m-CPP, an 5-HT2C agonist, considered as a reference compound, has the same affinities that medifoxamine, but a higher one for 5-HT2A (ratio = 3.42). In animals models considered as predictive for psychotropic activity in human, we investigate in rat the impact of medifoxamine on 5-HT2C receptors, using Learned-Helplessness model (LH) and the social interaction test.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:[The role of type 2 serotonin receptors, 5-HT2A and 5-HT2C, in depressive disorders: effect of medifoxamine]. 798 7

1-(3-Chlorophenyl)piperazine (m-CPP) (0.1-4 mg/kg s.c.) and N-(3-trifluoromethylphenyl)-piperazine (TFMPP) (0.5-4 mg/kg s.c.), 5-HT1C receptor agonists, but not 8-hydroxy-dipropylamino-tetralin (8-OH-DPAT) (0.1 and 0.2 mg/kg s.c.), a 5-HT1A receptor agonist, induced penile erection and yawning with a U-inverted dose-response curve in male rats. The maximal effect was found with 0.5 mg/kg s.c. of m-CPP and with 1 mg/kg s.c. of TFMPP. The m-CPP (0.5 mg/kg s.c.) and TFMPP (1 mg/kg s.c.) responses were prevented by mianserin (0.2 mg/kg s.c.) and by ritanserin (1 mg/kg s.c.) given 15 min before m-CPP and TFMPP. In contrast, m-CPP- or TFMPP-induced penile erection and yawning were not antagonized by haloperidol (0.1 mg/kg s.c.) or by [d(CH2)5Tyr(Me)2,Orn8]vasotocin (5 micrograms i.c.v.). Apomorphine- and oxytocin-induced penile erection, but not yawning, was also antagonized by mianserin and less effectively by ritanserin. The results suggest that 5-HT1C receptor agonist-induced penile erection and yawning are not mediated by increased dopaminergic and/or oxytocinergic transmission, and raise the possibility that a neuronal dopamine-oxytocin-5-HT link is involved in the control of penile erection and not necessarily of yawning in male rats.
 ...
PMID:Penile erection and yawning induced by 5-HT1C receptor agonists in male rats: relationship with dopaminergic and oxytocinergic transmission. 800 37

The relationship between serotonin neurotransmission and alcohol consumption (AC) was first determined in preclinical studies. AC generally increases following treatments which decrease serotonin activity, and levels of 5-HT and metabolites are low in some brain regions of alcohol-preferring rats. Pharmacological treatments which enhance serotonergic neurotransmission (uptake inhibitors, releasers, agonists) consistently reduce AC in rats. Serotonin uptake inhibitors (SUI; e.g., citalopram, fluoxetine) have been studied extensively in humans. In several double-blind randomized, placebo-controlled trials, SUI consistently decreased short-term (2-4 weeks) AC by averages of 15% to 20% in nondepressed mildly/moderately dependent alcoholics who received no other treatment. Some subjects decreased AC by up to 60%. The effects of SUI on AC were dose-dependent and not related to side effects (few and mild) or changes in anxiety or depression (not observed). SUI decreased desire to drink and liking for alcohol, suggesting a mechanism of action, to be considered in the development of treatments to reduce AC and prevent relapse. However, while an adjunctive brief psychosocial intervention enhanced the short-term effect of a SUI, the long-term (12-week) effects of SUI and placebo were similar. Other drugs acting on the 5-HT system have been tested in humans, but results are inconclusive. For example, buspirone, a 5-HT1A receptor partial agonist, reduced anxiety and alcohol craving, but not AC; a 5-HT partial agonist, m-CPP, increased craving in abstinent alcoholics; modest reductions in AC were observed with a 5-HT3 antagonist, ondansetron (0.5 mg/day, but not 4 mg/day). Ritanserin, a 5-HT2 antagonist, reduced desire to drink and prevented relapse in a small (n = 5) study, and there was some indication that it reduced desire to drink and enhanced alcohol effects without reducing AC, in another study. The therapeutic potential of these medications is being studied. SUI and other serotonin-altering medications are promising new neuropharmacological treatments for AC.
 ...
PMID:Serotonin-altering medications and desire, consumption and effects of alcohol-treatment implications. 803 52


<< Previous 1 2 3 4 5 6 7 Next >>