Serotonin and tolerance to delay of reward in rats

Rationale: Tolerance to delay of gratification. taken to reflect impulsiven ess; has been proposed to be under the preferential control of central sero tonin (5-HT) processes. Objective: The present study further examined the e ffects of drugs which directly or indirectly alter 5-HT transmission, on be haviour controlled by a delayed positive reinforcer. Methods: Rats were giv en the choice in a T-maze between two magnitudes of reward: small (two food pellets) and immediate versus large (ten pellets) but delayed. When a 15-s waiting period was imposed in the arm leading to the large reward, rats se lected this arm on 65-70% of the trials. This frequency was reduced to less than 40% when the large reward was delayed by 25 s. Results: In rats whose ascending 5-HT pathways had been lesioned by infusion of 5,7-dihydroxytryp tamine (5,7-DHT) into the dorsal raphe, the introduction of the 15-s delay contingency resulted in a transient larger reduction of the frequency of ch oice of the now-delayed reward, compared to sham operated controls. In cont rast, choice behaviour of rats given 5,7-DHT into the substantia nigra did not differ from controls. para-Chlorophenylalanine (pCPA, 150 mg/kg IP, dai ly for 3 days), a 5-HT synthesis inhibitor, bretazenil (0.5-8 mg/kg IP), a benzodiazepine (BZD) receptor partial agonist. and muscimol (0.25-1 mg/kg L P), a GABA(A) receptor agonist, induced a shift toward immediate reward. In contrast to the other BZDs, alprazolam (1-2 mg/kg IP) enhanced the frequen cy of choice of the large-but-25 s-delayed reward. Similar increased prefer ence for the large-but-delayed reward was induced by the selective 5-HT reu ptake inhibitors, fluoxetine (4-8 mg/kg IP) and fluvoxamine (4 mg/kg IP). T he full 5-HT1A receptor agonist, 8-OH-DPAT (0.015-0.5 mg/kg IP) enhanced th e frequency of choice of the large reward delayed by 25 s, whereas the part ial agonists, buspirone (1-4 mg/kg IP)I ipsapirone (0.5-1 mg/kg IP) and MDL 73005EF (1-2 mg/kg SC), and the antagonist, WAY 100635 (4 mg/kg SC), reduc ed the number of choices of the large reward delayed by 15 s. Unexpectedly, WAY 100635 (2 mg/kg). which had no effect on choice whatever the delay, di d not counteract the increased tolerance to delay induced by 8-OH-DPAT (0.0 6 mg/kg) and further reduced the frequency of choice of the large-but-15 s- delayed reward induced by ipsapirone (0.5 mg/kg). Conclusions: These effect s on tolerance to delay may be accounted for by a subtle balance between th e opposing functional consequences of pre- versus post-synaptic 5-HT1A rece ptor activation or blockade. Overall, the present results provide further s upport to the idea that 5-HT processes participate in the control of impuls ive-related behaviour, as assessed from tolerance to delay of reward in thi s particular T-maze procedure.