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

Several behaviors associated with the serotonin syndrome have been reported in rats following administration of the 5-HT1A receptor agonist 8-OH-DPAT. The present investigation approached this phenomenon from an ethopharmacological perspective, and provided a detailed temporal analysis of the behavioral effects of this compound over a 2-h period, in both male and female rats in the home cage. In addition, in order to further characterize the nature of the forepaw-treading and locomotor elements, and assess the extent of influence of the physical characteristics of the test arena, this study provided a detailed analysis of these behaviors in both the home cage and a large oval runway. In the initial analysis, the data indicate a distinct chronological sequence of effects following 8-OH-DPAT treatment. For example, "flat back" activity and lower lip retraction were apparent within a few minutes post-injection, the former dissipating after about 30 min and being replaced as the prepotent response by a more general (curved back) locomotor enhancement, while the latter effect remained throughout the 2-h test period. Interestingly, there were reliable gender differences in terms of the onset and disappearance of several behavioral components, with females generally being more rapidly affected, but recovering earlier than males. The detailed analysis of locomotor activity and forepaw treading would suggest that the locomotor syndrome primarily involves forward movement, heavily guided by the physical environment. Furthermore, forepaw-treading would seem only to occur when an animal reaches a barrier and forward movement is briefly interrupted, as no reliable incidence of this behavior was observed in the open area of the test area. Together, these findings provide further characterization of the behavioral syndrome induced by 8-OH-DPAT, and indicate the importance of time post-administration, gender of the subject, and the physical characteristics of the test environment, when considering stereotypical drug effects.
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PMID:An ethopharmacological analysis of the behavioral effects of 8-OH-DPAT. 787 Oct 10

The affective mimetic responses of male Wistar rats with prior access to 6% ethanol in their home cages were observed during intraoral infusions of an equivalent alcohol solution. Ethanol preference in the home cage appeared unrelated to measures of aversion and ingestion in the taste reactivity tests in normal rats. Adrenalectomy, which significantly reduced home cage ethanol preference, failed to influence the taste reactions elicited by ethanol or water. On the other hand, treatment of intact rats with the 5-HT1A receptor agonist ipsapirone (2.5 mg/kg), a drug that also decreases ethanol drinking in two-bottle intake tests, did increase the duration of aversive groomings, whereas measures of ingestion remained unaffected. These results suggest that ipsapirone, but not adrenalectomy, may alter the palatability of ethanol; this perceptual change may partly underlie the ability of ipsapirone to reduce home cage alcohol drinking in the rat.
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PMID:Taste reactivity to ethanol in rats: influence of adrenalectomy or ipsapirone. 794 82

Investigations examining the influence of 5-HT1A receptors in murine agonistic and social behavior have reported either specific or nonspecific attenuation of offensive behavior. To clarify this situation, the effects of three 5-HT1A agonists were examined on isolation-induced aggression and social behavior in male mice. 8-OH-DPAT (0.025-1.25 mg/kg) increased social behavior, rearing, and digging. Offensive behavior was reduced, without concomitant sedation. Ipsapirone (0.1-10.0 mg/kg) reduced naso-nasal behavior, whilst enhancing stretched-attend behavior, cage-exploration, and rearing. Offensive and defensive behaviors were attenuated, without reductions in activity. MDL 73005 EF (0.25-8.0 mg/kg) reduced social behaviors, cage-exploration and rearing while maintenance behavior was increased. Offensive and defensive behaviors showed attenuation. Current results corroborate previous findings with respect to 5-HT1A receptor involvement in murine agonistic behavior and anxiety. Data also connote that the behavioral specificity of 5-HT1A ligands should be interpreted in terms of response competition rather than solely concomitant sedation.
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PMID:5-HT1A receptor influences on rodent social and agonistic behavior: a review and empirical study. 798 51

In view of conflicting results reported for 5-HT1A receptor involvement in murine social conflict, this study examined the effect of two compounds, SDZ 216-525 and (-)-pindolol, on agonistic and social behavior in male mice. In a resident-intruder paradigm, (-)-pindolol (1.0-20.0 mg/kg), a beta-adrenergic 5-HT1A/1B antagonist, significantly attenuated all agonistic behaviors across the dose range employed. Social behaviors showed significant decreases, while nonsocial cage exploration showed significant increases at all doses. Defensive evade was significantly attenuated at 20.0 mg/kg. SDZ 216-525 (0.025-1.0 mg/kg), a selective 5-HT1A antagonist, significantly attenuated offensive posturing and bite-attacks at 1.0 mg/kg, and all offensive behaviors nonsignificantly at the smaller doses tested. Rearing was significantly attenuated at 1.0 mg/kg, while cage exploration increased at this dose. Defensive and social behaviors remained largely unchanged. These results show that both compounds tested produced significant reductions in offensive behavior, with concomitant changes in defensive, social, and nonsocial behaviors. Results are discussed in relation to SDZ 216-525 and (-)-pindolol potential for the control of anxiety and agonistic behavior.
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PMID:Effects of (-)-pindolol and SDZ 216-525 on social and agonistic behavior in mice. 830 68

The role of 5-HT1, 5-HT2 and 5-HT3 receptors in the genesis of colonic motor alterations induced by emotional stress was evaluated in rats equipped with implanted nickel/chrome electrodes on the proximal colon and a catheter into the lateral ventricle of the brain. In control rats the frequency of colonic spike bursts increased from 7.6 +/- 1.3 to 16.8 +/- 1.3 per 10 min when the rats were placed in a test cage in which they had previously received electric footshocks. I.p. injection of methysergide (0.1 mg/kg) reduced by 54% the emotional stress-induced increase of colonic spike burst frequency, while a higher dosage (1 mg/kg) of methysergide had no effect. The i.p. injection of ketanserin (a 5-HT2 receptor antagonist, 0.1 and 1 mg/kg) or granisetron (a 5-HT3 receptor antagonist, 0.1 and 1 mg/kg) had no effect on emotional stress-induced colonic hyperkinesia. The i.p. injection of the 5-HT1A receptor agonists, buspirone (1 mg/kg) or 8-OH-DPAT (8-hydroxy-2-(di-n-propylamino(tetralin) (0.05 and 0.1 mg/kg) or benzodiazepine (clonazepam, 1 mg/kg) significantly reduced or suppressed the emotional stress-induced increase of colonic spike bursts. Injected i.c.v., buspirone, but not 8-OH-DPAT, also reduced the emotional stress-induced hyperkinesia. Pretreatment with devazepide receptor (1 microgram/kg) antagonized the inhibitory effects of buspirone and 8-OH-DPAT injected i.p. on emotional stress-induced colonic hyperkinesia but did not alter the effects of clonazepam (1 mg/kg).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Comparative involvement of 5-HT1, 5-HT2 and 5-HT3 receptors in stress-induced colonic motor alterations in rats. 838 21

Interactions between central 5-HT1A receptors and the enantiomers of LY-41, a 2-aminotetralin derivative related to 8-OH-DPAT (8-hydroxy-2-(dipropylamino)tetralin), were studied. Both enantiomers of LY-41 behaved as potent 5-HT1A receptor agonists in rats, inducing the 5-HT behavioural syndrome, decreasing body temperature and inhibiting the cage-leaving response. The behavioural syndrome and the hypothermia were antagonized by the 5-HT1A receptor antagonist, (S)-UH-301. The LY-41 enantiomers also reduced brain 5-HTP accumulation in rats treated with a decarboxylase inhibitor. The pharmacology of the enantiomers of LY-41 appeared similar to that of 8-OH-DPAT. However, it is noteworthy that the stereoselective interaction of 5-HT1A receptors with LY-41 was opposite to that of 8-OH-DPAT. Thus, (R)-8-OH-DPAT was more potent than (S)-8-OH-DPAT, whereas (S)-LY-41 appeared to be more potent than (R)-LY-41.
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PMID:(R)- and (S)-8-acetyl-2-(dipropylamino)tetralin (LY-41): two novel 5-HT1A receptor agonists. 844 82

In group-housed mice (ten per cage), mice removed last from their home cage always have higher rectal temperatures than mice removed first from this cage. Stress-induced hyperthermia is calculated as the difference (delta T) between the basal temperature (mouse number 1) and the end temperature (mouse number 10) when the temperature of the ten mice is sequentially measured using a 1-min interval between rectal measurements. Using this protocol, various drugs, belonging to different pharmacological classes, were tested in order to investigate their putative anxiolytic effect, measured as a decrease in delta T. Benzodiazepines (diazepam, alprazolam), alcohol, and some (flesinoxan, buspirone), but not all (ipsapirone) 5-HT1A receptor agonists had anxiolytic properties with this protocol. Clonidine (alpha 2-adrenoceptor agonist) and prazosine (alpha 1-adrenoceptor antagonist) had, but at high doses, some anxiolytic actions. Antidepressants (desipramine, fluvoxamine, nomifensine, tianeptine, amitriptyline, clomipramine, imipramine), serotonergic ligands (ondansetron, ketanserin, 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI), fenfluramine, metachlorophenylpiperazine (mCPP), eltoprazine) and various other drugs (phenobarbital, pentetrazol, haloperidol, apomorphine, amphetamine, (+)-N-[1-methyl-2-oxo-5-phenyl-2,3-dihydro-1H-1,4-benzodiazepin-3( R)-yl]- N'-(3-methylphenyl)urea (MSD 365260), dizocilpine and acetyl salicylic acid) had no anxiolytic activity. The stress-induced hyperthermia protocol used was unable to detect anxiogenic properties of drugs, probably due to a (physiological) ceiling in the maximal end temperature. The stress-induced hyperthermia protocol with mice can be used to measure anxiolytic properties of drugs and is a fast and robust model which does not need extensive training of animals.
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PMID:Stress-induced hyperthermia as a putative anxiety model. 878 24

U-91356A [(R)-5,6-dihydro-5-(propylamino)4H-imidazo[4,5,1-ij]quinolin -2-(1H)-one, monohydrochloride], bound with highest affinity to the dopamine D2 receptor subtype, although it also bound with somewhat lower affinities to the dopamine D3 and D4, as well as the 5-HT1A receptor subtypes. In addition to depressing dopamine synthesis and turnover, injection of U-91356A increased striatal acetylcholine concentrations. U-91356A also depressed firing rates of dopamine neurons. In mice, this compound stimulated cage climbing and locomotor activity in reserpinized animals; it also antagonized D-amphetamine-stimulated locomotor activity. It produced contralateral turning in rats with unilateral lesions of the substantia nigra. These data are consistent with roles for the dopamine D2 receptor subtype as a dopamine autoreceptor and as a stimulatory, postsynaptic dopamine receptor.
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PMID:Pharmacology of U-91356A, an agonist for the dopamine D2 receptor subtype. 898 16

Racemic 8-OH-DPAT, (R,S)-8-hydroxy-2-(di-n-propylamino)tetralin, has become the prototype 5-HT1A receptor agonist. The enantiomers of 8-OH-DPAT have similar affinities to the 5-HT1A receptor, but the (R)-enantiomer is a full agonist, whereas the (S)-enantiomer is a partial agonist. This communication describes the dose- and time-response relationships of behavioural (5-HT behavioural syndrome, cage-leaving response), physiological (body temperature) and biochemical (5-HT turnover, 5-hydroxytryptophan accumulation) effects of (R)-8-OH-DPAT in rats. A high-performance liquid chromatography (HPLC)-UV method for determination of plasma and brain concentrations of (R)-8-OH-DPAT was developed, permitting studies of the pharmacokinetics of the drug. The concentrations of 8-OH-DPAT in brain were several fold higher than in plasma, and there were large variations in (R)-8-OH-DPAT concentrations between brain regions (highest in the hippocampus). (R)-8-OH-DPAT peaked in plasma at 5 min and in brain at 15 min after subcutaneous administration. The 5-HT1A behavioural syndrome peaked within 5 min after administration and disappeared after 30 min, when brain concentrations were still high. The hypothermic and biochemical responses developed gradually and were maximal at 45-60 min post injection, when both plasma and brain concentrations were declining. Thus, there was not a simple relationship between the kinetics and the dynamics of (R)-8-OH-DPAT. These results prompt further studies on the pharmacokinetics of 8-OH-DPAT within the central nervous system.
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PMID:Pharmacokinetic and pharmacodynamic studies of (R)-8-hydroxy-2-(di-n-propylamino)tetralin in the rat. 921 74

The behavioral effects of 8-OH-DPAT [0.5-10 mg/kg intraperitoneally (i.p.)] and (+) S-20499 (1-20 mg/kg IP), a recently synthesized 5-HT1A receptor full agonist, were examined over a 2-h period in mice in a neutral cage and, during the peak period of effect, in a runway, 8-OH-DPAT (1 and 10 mg/kg) and (+) S-20499 (10 and 20 mg/kg) blocked vertical activity (i.e., rearing and hanging on the wire mesh) during the period postinjection when levels of activity of the control mice were high. In this initial period (0-30 min), mice treated with 8-OH-DPAT, but not those treated with (+) S-20499, displayed flat back rather than curve back locomotion (0.5-10 mg/kg). However, after about 50 min., marked hyperactivity emerged for 8-OH-DPAT at 0.5 and 1 mg/kg and for (+) S-20499 at all doses, including increases in rearing, hanging, grooming, and for (+) S-20499, curve back locomotion. Both 8-OH-DPAT (10 mg/kg) and (+) S-20499 (> 20 mg/kg) significantly enhanced eating responses. Both drugs rapidly induced straub tail responses at all doses, and this effect remained significant until the end of the experiment at the highest doses. Subjects treated with 0.5 mg/kg of 8-OH-DPAT and 10 mg/kg of (+) S-20499 displayed in the initial time period "ballistic-type" rapid forelimb movements targeted toward the side of the head. During peak drug effect periods, higher doses of both drugs produced significant increases in movement with a change of direction, including rotation around the hindlimbs, suggesting, as do the ballistic-type movements, particular involvement of the forelimbs. These findings provide evidence consonant with the view that selective activation of 5-HT1A receptors in mice produces distinct behavioral changes in part associated with the 5-HT syndrome. Moreover, these changes differ, in the specific movements induced and in the drug parameters and time course of changes, from those reported in the laboratory rat.
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PMID:An ethopharmacological analysis of selective activation of 5-HT1A receptors: the mouse 5-HT1A syndrome. 925 22


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