Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:Q86TM3 (cage)
 29,987 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This paper demonstrates the application of an assay design that is particularly valuable for estimating receptor number (Bmax values) and affinity (Kd values) in many small samples of tissue. It is illustrated by its application to a study of possible circadian rhythms in the numbers of 5HT2 receptors in the rat cerebral cortex. The assay design involves the use of only two radioligand concentrations, the lower one being close to Kd (estimated from pilot studies) and the upper one close to 4 times this concentration. The results show that chronic clorgyline (1 mg/kg/day/28 days) administration to rats results in an 18% decrease in the number of cortical 5HT2 receptors (as measured by specific [3H]ketanserin binding). There is no significant circadian rhythm in receptor number in either the control or the MAOI-treated group. There is however, evidence of co-variation between the pairs of control animals housed in the same cage, and interestingly, that this effect is abolished by treatment with the MAOI.
 ...
PMID:Circadian studies of 5HT2 receptors: effects of clorgyline administration. 317 65

The effects of FG5893 were evaluated by several different methods; rats were used as experimental animals. Receptor binding studies revealed that FG5893 (2-(4-(4,4-bis(4-fluorophenyl)butyl)-1-piperazinyl)-3-pyridinecarboxy lic acid methyl ester) binds with high affinity to both 5-HT1A (Ki = 0.7 nM) and 5-HT2A receptors (Ki = 4.0 nM) but has only low affinity for the 5-HT2C receptor (Ki = 170 nM). FG5893 dose dependently reduced body temperature, and this effect was inhibited by pretreatment with (+/-)-pindolol. FG5893 (0.1 mg/kg) significantly inhibited head twitch behaviour induced by DOI (1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane) and FG5893 was also a potent inhibitor of ultrasound vocalization in rat pups (0.3 mg/kg) and of a passive avoidance response (0.1 mg/kg) in mature animals. FG5893 inhibited the cage-leaving response and induced part of the 5-HT behavioural syndrome, but only at very high doses (5 and 10 mg/kg, respectively). At increased doses (1 mg/kg), FG5893 also elicited corticosterone release and reduced the immobility time in the forced-swim test (1 mg/kg). Together, these data indicate that the mixed 5-HT1A receptor agonist/5-HT2A receptor antagonist FG5983 is a potent stimulator of presynaptic 5-HT1A receptors but is less active at the postsynaptic site. FG5893 had potent anxiolytic-like effects both on separation-induced ultrasound vocalization in rat pups and on a passive avoidance response. At increased doses, FG5893 possessed an antidepressant-like property.
 ...
PMID:Preclinical pharmacology of FG5893: a potential anxiolytic drug with high affinity for both 5-HT1A and 5-HT2A receptors. 781 50

The atypical antipsychotic drug clozapine interacts with multiple transmitter systems, among them the D4 subtype of dopamine receptors. PNU-96415E is chemically unrelated to clozapine and has its highest binding affinity for the D4 and 5-HT2A receptors. In comparison to clozapine, PNU-96415E is weaker in binding to D1, D2, alpha1 and muscarinic receptors. PNU-96415E inhibited exploratory locomotor activity in mice and rats, and antagonized d-amphetamine-induced locomotor stimulation in rats. It antagonized apomorphine-induced cage climbing, and blocked head and body twitch produced by 5-HTP in mice. Like clozapine, but unlike haloperidol, PNU-96415E did not antagonize stereotypic behaviors produced by a high dose of d-amphetamine or methylphenidate in rats and mice. PNU-96415E blocked conditioned avoidance in rats but produced no catalepsy, a pattern similar to clozapine but different from haloperidol. In rats trained to discriminate clozapine from saline injections, the stimulus effect generalized completely with PNU-96415E, but not haloperidol. This profile of pharmacological activities is consistent with that of an atypical antipsychotic and, as in the case with clozapine, the behavioral effects of PNU-96415E cannot be ascribed to a single receptor mechanism.
 ...
PMID:PNU-96415E, a potential antipsychotic agent with clozapine-like pharmacological properties. 910 28

Forty-five male Wistar rats were selected according to their behavior in the elevated plus-maze. They were separated as follows: animals with low exploratory activity ('anxious'), an 'intermediate' group and animals having high exploratory activity ('non-anxious'). Various receptor binding studies and hormonal assays were also performed in these selected rats. The affinity of 5-hydroxytryptamine 5-HT2A receptors in the frontal cortex was lower in the 'anxious' rats compared to home-cage controls and 'non-anxious' animals. Moreover, the number of cholecystokinin (CCK) receptors in the hippocampus was significantly elevated in the 'anxious' group compared to home-cage control animals. The blood levels of growth hormone (GH) were significantly lower in the 'non-anxious' rats compared to 'anxious' counterparts. In conclusion, it seems likely that the decreased exploratory activity of rats is related to the increased 5-hydroxytryptamine (5-HT) and CCK mediated neurotransmission in the brain. The different serum levels of GH in the selected rats probably reflect alterations in the activity of 5-HT and CCK.
 ...
PMID:Relation of exploratory behavior of rats in elevated plus-maze to brain receptor binding properties and serum growth hormone levels. 944 61

1. The present study examined 5-HT2C receptor agonist-induced behavioural tolerance and 5-HT2C receptor down-regulation in adult rat brain. The effect of chronic subcutaneous infusion of the 5-HT2C receptor agonist, m-chlorophenylpiperazine (m-CPP, 10 mg kg(-1), day(-1)), for 14 days was examined on daily food intake, the ability of acute m-CPP (2.5 mg kg(-1), i.p.) to induce hypolocomotion in a novel arena and elevate plasma corticosterone levels and on ex vivo cortical [3H]-mesulergine binding and hippocampal 5-HT2C receptor protein levels. 2. Before chronic infusion, m-CPP (2.5 mg kg(-1), i.p.) attenuated the number of turns and rears made in a novel open field arena. In contrast, while m-CPP still elicited this hypolocomotion following 14 days, saline infusion, no such hypolocomotion occurred in rats given chronic m-CPP (10 mg kg(-1) day(-1)), indicating that almost complete tachyphylaxis of this behaviour occurred with chronic 5-HT2C receptor agonist injection. 3. During chronic infusion of m-CPP, rats consumed less food per day than saline-treated controls. Acute challenge with m-CPP following two weeks, treatment still attenuated food intake over the next four hours (by 43% and 30%, respectively from that on the previous day) in saline and m-CPP infusion groups, showing that only partial tolerance to 5-HT2C receptor agonist-induced hypophagia occurred. 4. In naive home cage rats, plasma corticosterone was elevated in a dose-dependent manner 35 min after m-CPP injection (0.5, 1 and 3 mg kg(-1), i.p.) but levels were comparable to control values 16 h after m-CPP (2, 5 and 10 mg kg(-1), i.p.). Sixteen hours after a single m-CPP injection (2.5 mg kg(-1), i.p.), plasma corticosterone levels were comparable in a group of rats which had received 14 days infusion of m-CPP or saline. However, following a similar acute m-CPP injection (2.5 mg kg(-1), i.p., - 16 h) in rats previously infused for 14 days with m-CPP, plasma corticosterone levels were lower than those in a separate group which received no chronic infusions (but only acute m-CPP injection), even though the plasma m-CPP levels were comparable in both groups. The data are consistent with the proposal that chronic m-CPP induced some down-regulation of hypothalamic 5-HT2C receptors which contribute, in a tonic manner, to plasma corticosterone secretion under the conditions investigated. 5. Chronic m-CPP infusion reduced the amount of [3H]-mesulergine binding (by 27%, without altering the KD) in membranes prepared from parietal/occipital/temporal cortex (under conditions to exclude binding to 5-HT2A receptors) and 5-HT2C receptor protein-like immunoreactive levels measured by radioimmunoassay in the hippocampus by 38%, confirming that 5-HT2C receptor down-regulation had occurred. 6. Even after 14 days m-CPP infusion only partial behavioural tolerance and 5-HT2C receptor down-regulation were observed, which may vary in different brain regions of the rat. Thus the hypophagia produced by m-CPP may involve activation of 5-HT2C receptors in the hypothalamus, where there is a greater receptor reserve or which are more resistant to agonist-induced down-regulation than 5-HT2C receptors in limbic areas (striatum and nucleus accumbens) mediating m-CPP-induced hypolocomotion.
 ...
PMID:Effect of chronic m-CPP on locomotion, hypophagia, plasma corticosterone and 5-HT2C receptor levels in the rat. 960 79

Rats were given two weeks of home cage access to either "near-beer" (a beverage that tastes like beer but contains <0.5% ethanol v/v) or near-beer with added ethanol (4.5% v/v), which is simply referred to as "beer". The two groups of rats (near-beer and beer) were then trained on a "lick-based progressive ratio paradigm" in operant chambers in which an ever increasing number of licks had to be emitted for each successive fixed unit of near-beer or beer delivered. Break points (the ratio at which responding ceased) for near-beer and beer were approximately equal under baseline conditions. Rats were then tested for the effects of the 5HT2A/2C receptor antagonist ritanserin (0.625, 2.5 or 10 mg/kg), the opioid receptor antagonist naloxone (0.625, 2.5 or 10 mg/kg) or the cannabinoid CB1 receptor antagonist SR 141716 (0.3, 1 or 3 mg/kg). All three drugs caused a dose-dependent reduction of break-points and locomotor activity in both the beer and near-beer groups. However, the effects of SR 141716 and naloxone, but not ritanserin, on breakpoints were significantly more pronounced on rats drinking beer compared to those drinking near-beer. There were no such differential effects of any of the drugs on locomotor activity across the two groups. These results suggest that both SR 141716 and naloxone differentially affect the motivation to consume alcoholic beverages and may thus have potential as drugs for the treatment of alcohol craving.
 ...
PMID:The motivation for beer in rats: effects of ritanserin, naloxone and SR 141716. 1020 23

We have previously observed that intracerebroventricular infusion of a 5-HT2A receptor antisense oligonucleotide for 8 days results in an increase in cortical 5-HT2A receptor sites and an increase in central 5-HT2A receptor function as measured by quantitation of 5-HT2A receptor-mediated headshake behavior (28). Because lesioning serotonergic neurons or chronic administration of 5-HT2A receptor antagonists does not result in an increase in 5-HT2A receptor density or function in the brain, we have taken advantage of this unique upregulation of 5-HT2A receptors following 5-HT2A receptor antisense oligonucleotide infusion to study the modulation of D1 receptor-mediated behaviors by 5-HT2A receptors. Grooming behavior, elicited by acute injection of SKF 38393, was attenuated after chronic ICV infusion of a 5-HT2A receptor antisense oligonucleotide. There was also a reduction in vacuous chewing behavior induced by SKF 38393, which did not reach statistical significance. Other oral behaviors (i.e., tongue protrusions and gnawing at the cage bottom) were not attenuated. An increase in the density of cortical, as well as striatal 5-HT2A receptor sites was observed following chronic antisense oligonucleotide administration. There was no change in striatal D1 dopamine receptors following 5-HT2A receptor antisense oligonucleotide administration. SKF 38393-induced grooming behavior was also attenuated in naive rats pretreated acutely with the 5-HT2 receptor agonist DOI. These results suggest a role for the 5-HT2A receptor in the modulation of D1 receptor function.
 ...
PMID:Serotonin2A receptor modulation of D1 dopamine receptor-mediated grooming behavior. 1037 57

Placing of receptive females in the sector of a cage separated by a partition preventing physical contact but allowing sight and olfaction induced increases in blood testosterone levels in male mice. The selective agonist of 5-HT1A receptors 8-OH-DPAT (0.1 mg/kg) and the mixed 5-HT1A/1B receptor agonist eltoprazine (3.0 and 10.0 mg/kg) blocked the activatory effect of presentation of females on the hypothalamohypophyseal-testicular complex (HHTC) in males, while the 5-HT1A receptor antagonist p-MPPI (0.2 mg/kg) prevented the inhibitory effects of 8-OH-DPAT and eltoprazine. The 5-HT1B receptor agonist CGS-12066A (1.0 and 2.0 mg/kg) had no effect, while the mixed 5-HT1B/2C agonist TFMPP (5.0 mg/kg) blocked the increase in blood testosterone in males in response to presentation of females. The 5-HT2A receptor antagonist ketanserin (1.0 and 2.0 mg/kg) prevented the increase in testosterone induced by the presence of females. The 5-HT3 receptor antagonist ondansetron (0.05 and 0.1 mg/kg) increased the initial plasma testosterone level but blocked activation of the HHTC induced by the presence of receptive females. These results led to the conclusion that 5-HT receptors are involved in controlling the sexual activation of males. Different types and even subtypes of the same type of 5-HT receptor had different effects, both inhibitory and activatory, on activation of the HHTC by receptive females. Blockade of HHTC activation induced by the presence of females appears to involve 5-HT1A and 5-HT2C receptors, while activation involves 5-HT2A and 5-HT3 receptors.
 ...
PMID:The roles of different types of serotonin receptors in activation of the hypophyseal-testicular complex induced in mice by the presence of a female. 1558 14

The objective of the present study was to assess the role of the 5-HT2A/2C receptor at two specific brain sites, i.e., the dorsal periaqueductal gray matter (DPAG) and the medial septal (MS) area, in maternal aggressive behavior after the microinjection of either a 5-HT2A/2C receptor agonist or antagonist. Female Wistar rats were microinjected on the 7th postpartum day with the selective agonist alpha-methyl-5-hydroxytryptamine maleate (5-HT2A/2C) or the antagonist 5-HT2A/2C, ketanserin. The agonist was injected into the DPAG at 0.2 (N = 9), 0.5 (N = 10), and 1.0 microg/0.2 microl (N = 9), and the antagonist was injected at 1.0 microg/0.2 microl (N = 9). The agonist was injected into the medial septal area (MS) at 0.2 (N = 9), 0.5 (N = 7), and 1.0 microg/0.2 microl (N = 6) and the antagonist was injected at 1.0 microg/0.2 microl (N = 5). For the control, saline was injected into the DPAG (N = 7) and the MS (N = 12). Both areas are related to aggressive behavior and contain a high density of 5-HT receptors. Non-aggressive behaviors such as horizontal locomotion (walking) and social investigation and aggressive behaviors such as lateral threat (aggressive posture), attacks (frontal and lateral), and biting the intruder were analyzed when a male intruder was placed into the female resident's cage. For each brain area studied, the frequency of the behaviors was compared among the various treatments by analysis of variance. The results showed a decrease in maternal aggressive behavior (number of bites directed at the intruder) after microinjection of the agonist at 0.2 and 1.0 microg/0.2 microl (1.6 +/- 0.7 and 0.9 +/- 0.3) into the DPAG compared to the saline group (5.5 +/- 1.1). There was no dose-response relationship with the agonist. The present findings suggest that the 5-HT2A/2C receptor agonist has an inhibitory effect on maternal aggressive behavior when microinjected into the DPAG and no effect when microinjected into the MS. Ketanserin (1.0 microg/0.2 microl) decreased locomotion when microinjected into the DPAG and MS, but did not affect aggressive behavior. We interpret these findings as evidence for a specific role of 5-HT2A/2C receptors in the DPAG in the inhibition of female aggressive behavior, dissociated from those on motor activity.
 ...
PMID:Maternal aggression in Wistar rats: effect of 5-HT2A/2C receptor agonist and antagonist microinjected into the dorsal periaqueductal gray matter and medial septum. 1596 86

Exposure to a novel environment is a stressor which modulates behavior, increases stress hormones and enhances the release of several neurotransmitters including serotonin (5-HT). Exposing rabbits to a novel environment significantly increases head-bob behavior but fails to alter either grooming or wet dog shakes compared with those observed in the home-cage. The goal of this study was to determine the role of 5-HT and its receptors in mediating novelty-elicited head-bob behavior. Reduction of central 5-HT levels after treatment with the serotonergic neurotoxin 5,7-DHT significantly decreased novelty-elicited head bobs by 40% compared with those in sham-lesioned rabbits, indicating that 5-HT mediates, in part, this behavior. Additionally, pretreatment with the 5-HT1A partial agonist and clinically used anxiolytic buspirone also significantly attenuated novelty-elicited head bobs. Pretreatment with the selective 5-HT2A antagonist M 100,907 significantly reduced novel environment-elicited head bobs by 40%. Furthermore, agonist-induced reduction of cortical 5-HT2A receptor density resulted in a significant 40% reduction in the number of head bobs elicited by the novel environment. These data demonstrate that rabbit head-bob behavior, an index of the response to novelty stress, is mediated, in part, by 5-HT activation of 5-HT2A receptors.
 ...
PMID:Behavioral response to emotional stress in rabbits: role of serotonin and serotonin2A receptors. 1791 49


1 2 Next >>