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

d-Amphetamine (DEX) and phencyclidine (PCP) increased motor activity in rats as measured in automated activity cages. Analysis of the stimulation indicated that both drugs increased horizontal activity (total activity), locomotion, and peripheral activity. However, DEX increased while PCP decreased the incidence of rearing. The ability of different drugs to antagonise DEX- and PCP-induced increases in total activity (called stimulation) was measured. Dopamine (DA) D1 receptor antagonists (SCH23390, NNC-01-0112) were 7-8 times more potent in blocking DEX than PCP. DA D2 receptor antagonists (raclopride, remoxipride, haloperidol) were only 1-2 times more potent against DEX-induced stimulation. Nonselective DA receptor antagonists were also tested. Chlorpromazine was more potent against DEX than against PCP. Buspirone and sertindole were slightly more potent in blocking PCP than DEX. Ritanserin (5-HT2 receptor antagonist) was inactive against both stimulants. 8-OH-DPAT (5-HT1A receptor agonist) potentiated the stimulant effects of DEX and PCP. Prazosin (alpha 1-adrenergic receptor antagonist) partially blocked both DEX and PCP. Most drugs tested depressed spontaneous motor activity. Remoxipride and sertindole, however, caused very little depression even at doses several times higher than those needed to block DEX or PCP. The data show clear pharmacological differences between DEX- and PCP-induced stimulation.
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PMID:Dopamine receptor antagonists block amphetamine and phencyclidine-induced motor stimulation in rats. 809 Aug 16

The present study examined the discriminative stimulus effects of the MDMA optical isomers administered at different presession injection intervals. In the first experiment, male Sprague-Dawley rats were trained in a two-lever, food-reinforced operant procedure to discriminate either (+)-MDMA (1.25 mg/kg) or (-)-MDMA (3.50 mg kg) at either 20 or 90 min following injection. Animals administered (+)-MDMA or saline 90 min before training sessions failed to attain the discrimination criteria after 73 training sessions, whereas (-)-MDMA successfully established discriminative stimulus control at both the 20 min and the 90 min postinjection intervals. (+)-Amphetamine did not substitute for either isomer, although a significant amount of drug-appropriate responding occurred in animals trained to discriminate (+)-MDMA at 20 min and (-)-MDMA at 90 min. Sch 39166 partially reduced the discrimination of (+)-MDMA at 20 min and (-)-MDMA at 90 min, although this effect was not dose dependent. Sch 39166 had no effect on animals trained to discriminate (-)-MDMA at 20 min. Haloperidol did not alter the discrimination of (+)-MDMA at 20 min but partially reduced the discriminative stimulus control of (-)-MDMA at 20 min and (-)-MDMA at 90 min. Fenfluramine substituted for both isomers of MDMA. Pirenpirone completely blocked the discriminative stimulus effects of (-)-MDMA at 20 min, although (+)-MDMA at 20 min and (-)-MDMA at 90 min were only partly blocked. WAY 100,135 had little effect on drug-appropriate responding; however, the discrimination of (+)-MDMA at 20 min was partly reduced by this 5-HT1A antagonist. In a second experiment, rats trained to discriminate (+)-MDMA (1.5 mg/kg) or (-)-MDMA (3.0 mg/kg) from saline were administered substitution tests with both isomers 20, 60, 90 and 120 min after injection. Results confirmed those of the first experiment that (+)-MDMA appears to have a shorter duration of action than (-)-MDMA. These results are discussed in light of the training doses employed.
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PMID:Time course analysis of the discriminative stimulus effects of the optical isomers of 3,4-methylenedioxymethamphetamine (MDMA). 930 Jun 12

Two reference substances were used in the present study. d-Amphetamine is a direct catecholamine-releasing agent which has a marked stimulant effect upon locomotor activity at low to moderate doses and induces stereotypy at higher doses. (+/-)8-Hydroxy-2-(di-n-propylamino)-tetraline [(+/-)8-OH-DPAT] is a selective 5-HT1A receptor agonist which produces a well-defined behavioral syndrome and a dose-dependent hypothermia. The first aim of this study was to validate that the d-amphetamine-induced activity monitored by telemetry correlated to that concomitantly measured in automated cages and complement these measures with an ethologically based direct observational technique. d-Amphetamine (2.5 and 5.0 micromol/kg s.c.) stimulated locomotion as assessed with radiotelemetry, in automatic cages and by observation. Accompanying these behavioral effects was a concurrent increase (assessed by radiotelemetry) in heart rate but not in blood pressure. The second part of this study examined the pharmacological effects of (+/-)8-OH-DPAT (0.09-6.1 micromol/kg s.c.) on behavior (observation and activity) and temperature and on the cardiovascular system. (+/-)8-OH-DPAT induced the classical serotonergic syndrome of lower lip retraction, forepaw treading, and flattened body posture (observation), and this was accompanied by a concomitant hypothermia (radiotelemetry). (+/-)8-OH-DPAT also induced a dose-dependent and significant decrease in heart rate for 50 min of the 1-h long observation period. This was not accompanied by an increase in blood pressure in spite of the increased activity as seen with all three methods. These results show that radiotelemetry can be used as a tool to measure activity, core temperature, and the cardiovascular parameters in animals that are less stressed than those that are restrained for similar more invasive measurements, and that this technique can be used in combination with others to produce a more complete ethogram of the animal's responses to pharmacological challenges.
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PMID:A pharmacological validation of radiotelemetry in conscious, freely moving rats. 1010 Apr 95