Effects of imipramine-like drugs and serotonin uptake blockers on delay of reward in rats. Possible implication in the behavioral mechanism of action of antidepressants.
This study investigated in rats the action of a variety of antidepressants in two behavioral models. In model 1, animals trained in a T-maze were allowed to choose between 2 magnitudes of reward: immediate but small reward (2 pellets) vs. a 25-sec delayed but large reward (10 pellets). Under this alternative, vehicle-injected rats selected the large-but-delayed reward in less than 40% of the trials. Desipramine 8 mg/kg, clomipramine 8 mg/kg, maprotiline 8 mg/kg, indalpine 2 to 4 mg/kg, zimelidine 8 to 16 mg/kg, nialamide 16 to 32 mg/kg and clenbuterol 0.03 to 0.06 mg/kg significantly increased the number of choices of the large-but-delayed reward. In model 2, rats were subjected to a fixed ratio 48 schedule of food reinforcement; after completion of a series of exactly 48 presses a food pellet was delivered, and if no further press occurred, a sequence of free pellets was initiated according to fixed, increasing intervals (from 5-80 sec). Pressing during the sequence stopped it and required the rat to complete again the fixed ratio 48 to be reinforced and to reintiate the sequence. Waiting for free reward was significantly lengthened by desipramine 8, clomipramine 16, indalpine 8, zimelidine 8 to 16, nialamide 32 and clenbuterol 0.007 to 0.06 mg/kg. These results suggest that, possibly through noradrenergic and serotonergic mechanisms, antidepressants markedly enhanced rats' ability to wait for food reward, an affect which might reflect the ability of these drugs to improve impulse control. The relevance of such a property in the therapeutic action of antidepressants remains to be delineated.
Inserm U 302, Département de Pharmacologie, Faculté de Médecine Pitié-Salpêtrière, Paris, France.
J C
JC
Bizot
M H
MH
Thiébot
C
C
Le Bihan
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P
Soubrié
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P
Simon
D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects*; D003216:Conditioning, Operant / Q000187:drug effects; D007099:Imipramine / Q000494:pharmacology*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012054:Reinforcement, Psychology; D012201:Reward / Q000187:drug effects*; D012702:Serotonin Antagonists / Q000494:pharmacology*; D014868:Water Deprivation
D000928:Antidepressive Agents; D012702:Serotonin Antagonists; D007099:Imipramine