The effects of selected antidepressant drugs on timing behaviour in rats.
It has been suggested that the increased reinforcement rate on a differential-reinforcement-of-low-rate of responding (DRL) schedule observed following acute antidepressant administration in the rat is due to an improvement in timing accuracy. The aim of the present work was to evaluate the effects of antidepressants in another schedule that requires accurate estimation of time intervals, the peak procedure. Three antidepressant drugs were tested, the tricyclic antidepressant imipramine (1.0-10.0 mg/kg, i.p.) and the 5-HT reuptake inhibitors, zimelidine (10.0-40.0 mg/kg, i.p.) and clomipramine (1.0-10.0 mg/kg, i.p.). For reference, the full benzodiazepine receptor agonist, diazepam (1.0-5.0 mg/kg, i.p.) and the psychomotor stimulant, d-amphetamine (0.5-1.5 mg/kg, s.c.) were also tested. All doses of d-amphetamine tested significantly increased lever-pressing rates, whereas all the other compounds induced significant decreases in lever-pressing rates. Overall, the time at which the maximal lever-pressing rate occurred was not altered by any of the compounds, suggesting that timing accuracy was not significantly affected by any of the compounds administered. The only exception was zimelidine (40.0 mg/kg), which reduced the time at which the maximal lever-pressing rate occurred, although lever-pressing rates were also significantly reduced at this dose. These data suggest that previously reported antidepressant-induced improvement in performance on the DRL schedule may not have been due to improved timing accuracy per se but may have been due to a decrease in lever-pressing rates.
Bayley
P J
PJ
Merck Sharp and Dohme Research Laboratories, Neuroscience Research Centre, Harlow, Essex, UK.
Bentley
G D
GD
Dawson
G R
GR
D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D002997:Clomipramine / Q000494:pharmacology; D003216:Conditioning, Operant / Q000187:drug effects*; D007099:Imipramine / Q000494:pharmacology; D008297:Male; D051381:Rats; D015031:Zimeldine / Q000494:pharmacology
D000928:Antidepressive Agents; D015031:Zimeldine; D002997:Clomipramine; D007099:Imipramine