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)

Schedules which selectively reinforce low rates of responding (DRL, differential reinforcement of low rate) distinguish between antidepressants and other types of drugs. In a DRL schedule a subject is required to pause for a specified minimum period of time between two consecutive responses in order to obtain a reinforcer. The dependent variables are rate of responding and rate of reinforcement. Response patterns of rats treated with clinically effective antidepressant drugs such as imipramine (2.0-32.0 mg/kg) or fluvoxamine (4.0-32.0 mg/kg) are characterized by a decrease in response rate and an increase in reinforcement rate. Treatment with the 5-HT1A agonist flesinoxan (0.1-3.0 mg/kg) also dose-dependently decreased response rates while at the same time increasing reinforcement rates. Chlordiazepoxide (2.5-20.0 mg/kg) and diazepam (0.25-2.0 mg/kg) had no effects in the present experiment. d-Amphetamine increased response rates at low doses (0.5-2.0 mg/kg), and decreased it at the higher doses (4.0 mg/kg), but reinforcement rates were unaltered. Overall analysis of the effects of haloperidol (0.02-0.32 mg/kg) showed decreased responding and increased reinforcement rates. Post hoc analysis, however, clearly differentiated between haloperidol's profile and that of the antidepressants. As such, the results of the present experiment show that flesinoxan might possess antidepressant activity in humans.
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PMID:Flesinoxan shows antidepressant activity in a DRL 72-s screen. 135 3

Wistar rats can develop a high preference for 3% alcohol after a period of forced alcohol exposure and 2 days of alcohol withdrawal. If these rats are selected at a medium (> or = 60%) and a high (> or = 85%) level of alcohol preference, it is possible to study the effects of various compounds on alcohol intake and alcohol preference in rats with two different levels of alcohol preference. With this procedure, it was demonstrated that the benzodiazepine chlordiazepoxide can reduce alcohol preference at doses > or = 10.0 mg/kg in the high alcohol preference group, by increasing the water consumption without affecting alcohol drinking. Chlordiazepoxide had no effects in the medium alcohol preference group. The 5-HT uptake inhibitors fluoxetine and citalopram reduced alcohol intake and alcohol preference in both the medium and the high alcohol preference groups by means of a reduction in consummatory behaviour. Both drugs clearly affected total fluid intake and body weight gain. The 5-HT1A agent buspirone reduced alcohol intake and alcohol preference in the group of medium alcohol preferring rats at doses between 0.0025 and 0.63 mg/kg. The drug did not change water drinking so that total fluid consumption diminished. At doses > or = 2.5 mg/kg buspirone, there was an increased alcohol consumption. Buspirone was without important effects on the high alcohol preferring rats. The 5-HT3 antagonist ondansetron reduced alcohol intake in both the medium and high alcohol preferring rats at doses between 0.01 and 0.16 mg/kg. The drug had no effects on alcohol preference and water consumption. At some doses, there was a reduction in total fluid intake. The 5-HT2/1C antagonist ritanserin reduced alcohol intake and alcohol preference at doses between 0.04 and 2.50, and 0.16 and 10.0 mg/kg in the medium and high alcohol preferring rats, respectively. Together with the decrease in alcohol consumption there was an increase in water drinking, leaving total fluid intake unaffected. The activity of ritanserin was less pronounced in the high as compared to the medium alcohol preference group. These results indicate that various serotonergic agents can affect alcohol intake and alcohol preference by different mechanisms of action.
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PMID:Effects of various serotonergic agents on alcohol intake and alcohol preference in Wistar rats selected at two different levels of alcohol preference. 851 86

In a modified Geller-Seifter conflict procedure, rats were trained to lever-press for food under a multiple variable interval-fixed ratio (VI30: food; FR10: food + shock) schedule of reinforcement. The ability to antagonize response suppression in the punished period is considered a good predictor for anxiolytic activity. Chlordiazepoxide and alprazolam increased punished responding. The 5-HT1A receptor agonists flesinoxan (R(+)-N-[2[4-(2,3-dihydro-2-2-hydroxymethyl-1,4-benzodioxin-5-yl)- 1-piperazinyl]ethyl]-4-fluorobenzoamide; 0.1-10.0 mg/kg) and 8-OH-DPAT (8-hydroxy-2-(di-n-propyl-amino)tetralin; 0.03-0.5 mg/kg) significantly increased punished responding, supporting a role of the 5-HT1A receptor in anxiety. 8-OH-DPAT and flesinoxan also reduced unpunished responding. The anxiolytic effects of 8-OH-DPAT and flesinoxan could only be antagonized with a high dose (1.0 and 3.0 mg/kg respectively) of the 5-HT1A receptor antagonist WAY-100635 (N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl) cyclohexanecarboxamide trihydrochloride). All doses of WAY-100635 antagonized the 5-HT1A-induced effects on unpunished responding. The dissimilarity in dose-response curve of WAY-100635 on punished and unpunished behaviour poses questions about the mediation of these effects.
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PMID:Effects of 5-HT1A receptor ligands in a modified Geller-Seifter conflict model in the rat. 916 58

Anxiolytic-like activity in the mouse elevated plus-maze has recently been demonstrated for a range of compounds varying in degree of selectivity as 5-HT1A receptor antagonists. As tolerance and dependence liability are among the major clinical disadvantages of benzodiazepine therapy, the present study examined the effects of acute drug challenge on the plus-maze profiles of mice following daily treatment for 20 days with saline, chlordiazepoxide (CDP; 10.0 mg/kg) or the selective 5-HT1A receptor antagonist, WAY 100635 (0.1-1.0 mg/kg). To assess the development of physical dependence (withdrawal anxiogenesis), the study incorporated independent groups of animals tested on the maze 24 h after the final dose. Challenge with CDP or WAY 100635 produced behavioural changes indicative of anxiety reduction in mice that had received daily handling/saline for 20 days, thereby demonstrating that the chronic injection regimen per se had not compromised the acute efficacy of either agent. The absence of a similar response to acute drug challenge in mice treated chronically with CDP or WAY 100635 suggested the development of tolerance to the acute anxiolytic effects of both compounds under present test conditions. Despite these observations, however, no signs of enhanced anxiety were evident 24 h following discontinuation of chronic treatment with either compound. In a further experiment, the absence of withdrawal anxiogenesis at 24 h was replicated and extended to discontinuation periods of 36 and 48 h for both drugs. Although present results show that tolerance develops to the acute anxiolytic effects of CDP and WAY 100635 in the murine plus-maze, they also suggest that enhanced anxiety is not an inevitable consequence of abrupt cessation of chronic treatment with either compound.
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PMID:Tolerance to acute anxiolysis but no withdrawal anxiogenesis in mice treated chronically with 5-HT1A receptor antagonist, WAY 100635. 988 17

The effects of buspirone were tested on rearing in an open field. Six different doses of buspirone (10, 3.3, 1.1, 0.3, 0.1 and 0.04 mg/kg) and a single dose of chlordiazepoxide (5 mg/kg) were administered i.p. to separate groups of rats. Buspirone produced a dose-dependent decrease in rearing in the range 0.04-10 mg/kg, whereas only the higher doses (10 and 3.3 mg/kg) decreased ambulation significantly. Chlordiazepoxide reduced rearing to an extent equivalent to 1 mg/kg of buspirone. Together with data in the literature, the results suggest that 5-HT1A agonists affect rearing at lower doses than ambulation; that the effects of buspirone in the open field are similar to classical anxiolytics; and that changes in rearing may be more closely related to anxiolytic than muscle relaxant, anti-convulsant and other GABA-mediated effects of the classical anxiolytics.
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PMID:Dose-response analysis of the effects of buspirone on rearing in rats. 2228 22