Flesinoxan shows antidepressant activity in a DRL 72-s screen.
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.
van Hest
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Department of Pharmacology, SOLVAY-DUPHAR b.v., Weesp, The Netherlands.
van Drimmelen
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M
Olivier
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D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D014150:Antipsychotic Agents / Q000494:pharmacology; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D003216:Conditioning, Operant / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D006993:Hypnotics and Sedatives / Q000494:pharmacology; D008297:Male; D010879:Piperazines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012055:Reinforcement Schedule
D000928:Antidepressive Agents; D014150:Antipsychotic Agents; D000697:Central Nervous System Stimulants; D006993:Hypnotics and Sedatives; D010879:Piperazines; C056895:flesinoxan