Delay aversion: effects of 7-OH-DPAT, 5-HT1A/1B-receptor stimulation and D-cycloserine.
Impulsive individuals often display an aversion to waiting for rewards. Delay aversion can be quantified in rats in a delayed reward task, in which animals choose between an immediately available, small reward, and a large reward available after a delay. In previous research conducted at our laboratory and in literature, positive correlations between delay aversion and aggression, substance abuse and persistence during extinction of conditioned responses were found. The correlations suggest a possible shared pharmacology. Therefore, we tested drugs with known effects on these behaviors for possible effects on delay aversion: the dopamine D(3)-receptor agonist 7-OH-DPAT, the 5-HT(1A)-receptor agonist flesinoxan, the 5HT(1A/1B)-receptor agonist eltoprazine, and the NMDA-receptor agonist d-cycloserine. The results show that 7-OH-DPAT slightly decreased choice for the large reward. Flesinoxan disrupted task execution by lowering choice for the large reward even at a delay of 0 s. Eltoprazine slightly increased choice for the large reward, but the 5-HT(1B)-antagonist GR127935 had no effect. Administration of D-cycloserine also had no effect on choice behavior. The data suggest the dopamine D(3)-receptor and the 5-HT(1B)-receptor are interesting targets for treating delay aversion impulsivity. These targets were correctly predicted by the positive correlation between delay aversion and aggressive behavior and the intimate links between delay aversion and substance abuse disorders.
van den Bergh
Filip S
FS
Utrecht University, Department of Psychopharmacology, FAFC Wentgebouw, Kamer W124 Sorbonnelaan 16, 3584CA, Utrecht, Netherlands.
Bloemarts
Emilie
E
Groenink
Lucianne
L
Olivier
Berend
B
Oosting
Ronald S
RS
D000818:Animals; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D003523:Cycloserine / Q000627:therapeutic use*; D003913:Dextroamphetamine / Q000494:pharmacology; D007175:Impulsive Behavior / Q000523:psychology*; D008297:Male; D010069:Oxadiazoles / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D050637:Receptors, Dopamine D3 / Q000819:agonists*; D016194:Receptors, N-Methyl-D-Aspartate / Q000819:agonists* / Q000037:antagonists & inhibitors; D058825:Serotonin 5-HT1 Receptor Agonists; D058829:Serotonin 5-HT1 Receptor Antagonists; D013764:Tetrahydronaphthalenes / Q000494:pharmacology*
D000697:Central Nervous System Stimulants; D010069:Oxadiazoles; D010879:Piperazines; D050637:Receptors, Dopamine D3; D016194:Receptors, N-Methyl-D-Aspartate; D058825:Serotonin 5-HT1 Receptor Agonists; D058829:Serotonin 5-HT1 Receptor Antagonists; D013764:Tetrahydronaphthalenes; C090701:GR 127935; C056895:flesinoxan; C063828:eltoprazine; D003523:Cycloserine; C031349:7-hydroxy-2-N,N-dipropylaminotetralin; D003913:Dextroamphetamine