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)

A series of experiments was carried out to analyze the effects of the 5-HT1A agonists tandospirone or buspirone on the retention of fear conditioning in mice. Fear was produced by pairing tone and shock in a conditioned emotional response (CER) paradigm and strength of conditioning was assessed by measuring suppression of drinking in presence of tone. Fear conditioning was disrupted if tandospirone and buspirone were administered before the conditioning session but not before the test trial. Diazepam disrupted conditioning at both times. Tandospirone did not disrupt performance if conditioning was tested 1 hr rather than 24 hr after training, suggesting that disrupted memory rather than impaired acquisition was responsible for the deficit. The effect of tandospirone on fear conditioning could be reversed by administration of d-amphetamine prior to the retention test, which suggests that information was stored but is inaccessible to normal retrieval cues. Tandospirone and buspirone also retarded extinction, a clear indication that the disruption caused by these drugs is unrelated to their anxiolytic action.
 ...
PMID:5-HT1A agonists disrupt memory of fear conditioning in mice. 847 77

The effect of ipsapirone, a partial agonist at 5-HT1A receptors, and of diazepam on punished operant responding was studied in rats injected intracerebroventricularly with 150 microg 5,7-dihydroxytryptamine to deplete brain serotonin or pretreated with (S)-WAY 100135 (N-tert-butyl) 3-4-(2-methoxyphenyl)piperazin-1-yl-2-phenylpropanamide dihydrochloride), an antagonist at 5-HT1A receptors. 5,7-Dihydroxytryptamine markedly depleted brain serotonin and caused a sustained increase in punished responding with no effect on rates of unpunished responding in sham-operated rats but had no effect in animals which had received 5,7-dihydroxytryptamine. At 5 and 10 mg/kg ipsapirone reduced unpunished responding similarly in sham-operated and 5,7-dihydroxytryptamine-treated rats. Diazepam 2.5 mg/kg i.p.significantly increased punished responding and reduced rates of unpunished responding similarly in sham-operated and in 5,7-dihydroxytryptamine-treated animals. At 3 and 10 mg/kg (S)-WAY 100135 did not modify punished or unpunished responding but at 10 mg/kg it completely antagonized the effect of 5 mg/kg/s.c. ipsapirone on unpunished and punished responding. The results suggest that ipsapirone releases behaviour that is suppressed by punishment by stimulating presynaptic 5-HT1A receptors.
 ...
PMID:Presynaptic 5-HT1A receptors mediate the effect of ipsapirone on punished responding in rats. 866 6

In the stress-induced hyperthermia (SIH) paradigm in mice, both a benzodiazepine receptor agonist, diazepam, and a 5-HT1A receptor agonist, flesinoxan, reduced the stress-induced increase in rectal temperature. The SIH procedure itself enhanced plasma ACTH and corticosterone levels but not plasma glucose levels. Diazepam (3, 6, and 12 mg/kg p.o.) did neither affect basal plasma ACTH, corticosterone, or glucose levels, nor did it suppress the stress-induced rises in these parameters. Flesinoxan (1, 3, and 10 mg/kg p.o.) enhanced plasma ACTH and corticosterone concentrations under nonstress conditions but did not affect the stress-induced increases in ACTH and corticosterone secretion. No clear effects of flesinoxan on plasma glucose levels were found. Our results indicate that in mice the anxiolytic effects of diazepam and flesinoxan in the SIH paradigm are not paralleled by a blockade of stress-induced increases in plasma ACTH, corticosterone, and glucose levels.
 ...
PMID:Neuroendocrine effects of diazepam and flesinoxan in the stress-induced hyperthermia test in mice. 872 65

Our previous study showed that conditioned fear stress (CFS) increased serotonin (5-HT) metabolism in the medial prefrontal cortex and induced freezing behavior. Although these results could support the 5-HT hypothesis of anxiety, the functional significance of the 5-HT response to stress is unclear. In this study, the effects of 5-HT reuptake inhibitors, agonists, antagonists, and diazepam on freezing behavior induced by CFS were examined using a time-sampling procedure. Various doses of test compounds were administered subcutaneously to rats 24 h after the last session of repeated foot-shock for 5 days. Rats were again placed in the shock chamber without shocks 20 min after injections of drugs, and observed. Diazepam (1 mg/kg) and the 5-HT1A agonist ipsapirone (0.5-10 mg/kg) significantly inhibited freezing behavior. L-5-Hydroxytryptophan (with benserazide) and the selective 5-HT reuptake inhibitor citalopram (10 mg/kg) reduced freezing behavior. The 5-HT2 antagonists ICI169,369 and ketanserin failed to change freezing behavior. p-Chlorophenylalanine (200 mg/kg) administered 15 h before the test did not affect freezing. The effect of ipsapirone was not modified in rats with lesions of 5-HT neurons, produced by p-chloroamphetamine (2 x 10 mg/kg). In conclusion, these results suggest the anxiolytic potential of ipsapirone and citalopram, and support the hypothesis that the facilitation of 5-HT neurotransmission decreases anxiety.
 ...
PMID:Serotonergic activation reduces defensive freezing in the conditioned fear paradigm. 880 84

We evaluated the impact of conditioned stress on outflow of dopamine in the rat prefrontal cortex. Exposure of rats to an environment associated with aversive stimuli-foot shock enhanced outflow of dopamine in a similar way as seen during the conditioning session when foot shocks were applied. Diazepam (2.5 and 10 mg/kg) dose-dependently decreased outflow of dopamine and, when given in a dose of 10 mg/kg, but not 2.5 mg/kg, decreased enhanced dopamine outflow evoked by conditioned stress. On the other hand, ipsapirone (10 mg/kg, but not 2.5 mg/kg) and buspirone (2.5 mg/kg) enhanced basal outflow of dopamine. When ipsapirone (10 mg/kg) and buspirone (2.5 mg/kg) were given to rats exposed to conditioned stress, the stress-evoked elevation in dopamine outflow was abolished. Ipsapirone in a dose of 2.5 mg/kg was ineffective in the stress paradigm tested. It is concluded that conditioned stress in vivo enhances dopaminergic neurotransmission in the rat prefrontal cortex, this effect being attenuated by diazepam, a classic anxiolytic drug, and by such novel anxiolytics as ipsapirone and buspirone, which operate via serotonergic 5-HT1A receptors. Although ipsapirone and buspirone blocked stress-induced enhancement of dopamine outflow, this effect seems to result from their influence on the basal outflow of dopamine. Differential effects of diazepam and 5-HT1A agonists on basal and stress-induced alterations in dopamine outflow are discussed in terms of their possible effectiveness in various types of general anxiety disorders.
 ...
PMID:Evidence that conditioned stress enhances outflow of dopamine in rat prefrontal cortex: a search for the influence of diazepam and 5-HT1A agonists. 892 64

In the present study, the effects of 5-HT1A receptor ligands with varying degrees of intrinsic activity at the 5-HT1A receptor were examined in the conditioned emotional response (CER) test and their effects compared to those of the benzodiazepine receptor agonists, diazepam and chlordiazepoxide. Diazepam (3.0 mg/kg) and chlordiazepoxide (3.0 mg/kg), and the 5-HT1A receptor partial agonists, ipsapirone (10.0 mg/kg) and gepirone (3.0 mg/kg), alleviated conditioned suppression of lever pressing. The 5-HT1A receptor partial agonist, buspirone (0.1-1.0 mg/kg), the 5-HT1A receptor agonist, 8-OH-DPAT (0.01-0.10 mg/kg), and the 5-HT1A receptor antagonist, WAY-100635 (0.03-3.0 mg/kg), had no effects on conditioned fear. Neither enhancing the level of food deprivation nor pretreatment with the amnesic agent scopolamine induced anxiolytic-like effects in the present CER test. The anxiolytic-like effects of ipsapirone in this test were completely reversed by WAY-100635. These results indicate that 5-HT1A agonist, but not antagonist actions, induce an anxiolytic effect in the CER test in rats.
 ...
PMID:Effects of 5-HT1A receptor agonists, partial agonists and a silent antagonist on the performance of the conditioned emotional response test in the rat. 897 49

A method to measure various aspects of exploratory behavior was further characterized using standard pharmacological treatments known to induce anxiety, or anxiolysis, or locomotor activation. FG 7142, an anxiogenic beta-carboline, induced a dose-dependent reduction in the rat exploratory behavior. A single FG 7142 (20 mg/kg) treatment before behavioral testing had a carry-over effect on rats' behavioral performance on the two subsequent days. When FG 7142 (20 mg/kg) was administered during five consecutive days before behavioral testing, its anxiogenic-like effect first deepened, but waned off by the fifth session. Diazepam at the dose of 0.5 mg/kg had no effect of its own, but blocked the anxiogenic-like effect of FG 7142 (10 mg/kg) treatment. At a higher dose (1 mg/kg), diazepam treatment reduced exploratory behavior, but this effect was not carried over to the drug-free sessions on the subsequent day. Buspirone and gepirone (both 1 mg/kg), the 5-HT1A receptor agonists, had no effect. D-Amphetamine, a locomotion-enhancing drug which has anxiogenic-like properties in several tests of exploratory behavior, increased the activity of rats at the dose of 0.5 mg/kg, but at the dose of 1 mg/kg the only effect was a reduction in the number of rearings: this effect was not carried over to the subsequent retest. On the basis of the results described in this article and elsewhere, we suggest that this technique can be useful for separating a true anxiogenic drug from other compounds which influence exploratory activity.
 ...
PMID:Characterization of rat exploratory behavior using the exploration box test. 958 Apr 70

Effects of MKC-242 (5-[3-[((2S)-1,4-benzodioxan-2-ylmethyl)amino]propoxy]-1,3-b enzodioxole HC1), a novel 5-HT1A-receptor agonist, and reference compounds on wrap restraint stress-induced defecation were evaluated in rats. Wrapping restraint stress increased defecation in rats. The increase was attenuated by putative 5-HT1A-receptor agonists, MKC-242 and 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT). The suppressive effect of MKC-242 on wrap stress-induced defecation was antagonized by prior administration of a 5-HT1A-receptor antagonist, WAY100135. MKC-242 did not affect spontaneous defecation and 5-HT-induced defecation. Diazepam and amitriptyline also significantly reduced the stress-induced defecation. However, amitriptyline showed a potent anti-cholinergic effect in the oxotremorine-induced tremor test and reduced spontaneous defecation. In contrast to MKC-242 and 8-OH-DPAT, buspirone and tandospirone tended to suppress the increase at high doses. A major metabolite of buspirone and tandospirone, 1-(2-pyrimidinyl)piperazine, antagonized the suppressive effect of MKC-242. These findings suggest that stimulation of 5-HT1A receptors reduces stress-induced defecation but not spontaneous and 5-HT-induced defecation and that MKC-242 may be useful for the treatment of irritable bowel syndrome.
 ...
PMID:Reduction of wrap restraint stress-induced defecation by MKC-242, a novel benzodioxan derivative, via 5-HT1A-receptor agonist action in rats. 971 68

The effects of buspirone, fluvoxamine and diazepam were investigated, using healthy volunteers, in an aversive conditioning paradigm, a putative model for conditioned anxiety. The main prediction was that buspirone, an anxiolytic agent which reduces activity in serotonin (5-hydroxytryptophan, 5-HT) neurones, would attenuate aversively conditioned skin conductance responses. Skin conductance responses were recorded to 10 neutral tones (habituation phase). Tone 11 was immediately followed by a 1-s 90-dB aversive white noise (unconditioned stimulus). The conditioning trial reinstated responding to a second presentation of the tones (extinction phase). Skin conductance response amplitude, inter-response level and spontaneous fluctuations were recorded. There were five treatment groups comprising five men and five women. One control group took placebo, another control group received nothing; there was no effect of placebo on any measure. Diazepam (2 mg, p.o.), a positive comparator, markedly reduced the amplitude of skin conductance responses at all phases of the experiment, but only in women. Buspirone (5 mg, p.o.) had the predicted effect of accelerating extinction but also of unexpectedly accelerated habituation of skin conductance responses. There was a trend to reduce spontaneous fluctuations and no effect on skin conductance level. The effects of buspirone were thus specific to responses to stimuli. Fluvoxamine (25 mg, p.o.) had similar effects to buspirone and diazepam in women. An action common to buspirone, fluvoxamine and diazepam, which may account for their shared effect on conditioned autonomic responses, is the suppression of neural activity in the dorsal raphe nucleus. It is argued that enhanced habituation must involve a different mechanism, such as enhanced 5-HT1A function in the terminal fields of the median raphe nucleus.
 ...
PMID:Comparison of buspirone with diazepam and fluvoxamine on aversive classical conditioning in humans. 1047 16

Two new analogs of full 5-HT1A receptor antagonist 4-[3-(1-benzotriazolyl)propyl]-1-(2-methoxyphenyl)piperazine (MP 3022; 1) containing di- (5) or tetramethylene- (6) spacer were synthesized. In the radioligand binding studies, compounds 5 and 6 showed high 5-HT1A (Ki = 14.7 nM and 11.8 nM, respectively) and low 5-HT2 receptor affinity (Ki = 2,696 nM and 389.2 nM, respectively). In behavioral studies both compounds behaved like postsynaptic 5-HT1A receptor antagonists as they reduced lower lip retraction and behavioral syndrome induced by 8-OH-DPAT (5-HT1A receptor agonist) in rats, but 6 was more effective in these tests. Derivative 5 did not affect body temperature in mice, whereas 6 decreased it. Furthermore, 5 did not change hypothermia induced by 8-OH-DPAT, and 6-induced lowering of body temperature in mice was not antagonized by (S)-WAY 100135 (5-HT1A antagonist), so in that model 5 and 6 did not behave as antagonist or agonist, respectively, at presynaptic 5-HT1A receptors. Compound 6 was studied in behavioral tests used to predict a potential anxiolytic (conflict drinking test in rats) and antidepressant (forced swimming test in rats) activity. Diazepam and imipramine were used as reference drugs. Compound 6 significantly increased the number of shocks accepted in water-deprived rats in conflict drinking test and shortened the immobility time in forced swimming test in rats. The above findings indicate that new 5-HT1A postsynaptic antagonist 6 behaves like anxiolytic and antidepressant, but mechanisms of these properties of 6 remain unknown.
 ...
PMID:Some pharmacological properties of new analogs of MP 3022, the 5-HT1A receptor antagonist. 1081 41


<< Previous 1 2 3 Next >>