Acute Effects of d-Amphetamine on the Differential Reinforcement of Low-Rate (DRL)

Ruey-Ming Liao；Ruey-Kuang Cheng

D1 and D2 receptors ； IRT analysis ； ketamine ； pentylenetetrazole ； psychostimulant ； raclopride ； SCH23390 ； timing behavior

The Chinese Journal of Physiology

48卷1期（2005 / 03 / 01）

41 - 45

英文

Amphetamine and it analogs have been shown to affect operant behavior maintained on the differential reinforcement of a low-rate (DRL) schedule. The aim of the present study was to investigate what specific component of the DRL response is affected by d-amphetamine. The acute effects of d-amphetamine on a DRL task were compared with those of the selective dopamine D1 and D2 receptor antagonists, SCH23390 and raclopride, respectively. Pentylenetetrazole and ketamine were also used as two reference drugs for comparison with d-amphetamine as a psychostimulant. Rats were trained to press a lever for water reinforcement on a DRL 10-s schedule. Acute treatment of d-amphetamine (0, 0.5, and 1.0 mg/kg) significantly increased the response rate and decreased the reinforcement in a dose-related fashion. It also caused a horizontal leftward shift in the inter-response time (IRT) distribution at the doses tested. Such a shifting effect was confirmed by a significant decrease in the peak time, while the mean peak rate and burse response remained unaffected. In contrast, both SCH23390 (0, 0.05, and 0.10 mg/kg) and raclopride (0, 0.2, and 0.4 mg/kg) significantly decreased the total, non- reinforced, and burst responses. The de-burst IRT distributions were flattened out as shown by the dose-related decreases in the mean peak rate for both dopamine antagonists, but no dramatic shift in peak time was detected. Interestingly, neither pentylenetetrazole (0, 5, and 10 mg/kg) nor ketamine (0, 1, and 10 mg/kg) disrupted the DRL behavioral performance. It is then conceivable that d-amphetamine at the doses tested affects the temporal regulation of DRL behavior. The effectiveness of d-amphetamine is derived from its drug action as a psychostimulant. Taken together, these data suggest that different behavioral components of DRL task are differentially sensitive to pharmacological manipulation.

1. Balcells-Olivero, M.,Richards, J.B.,Seiden, L.S.(1997).Sensitization to amphetamine on the differential-reinforcement-of-low-rate 72-s schedule.Psychopharmacology,133,207-213.
2. Bizot, J.-C.(1998).Effects of various drugs including organophosphorus compounds (OPC) and therapeutic compounds against OPC on DRL responding.Pharmacol. Biochem. Behav.,59,1069-1080.
3. Britton, K.T.,Koob, G.F.(1989).Effects of corticotropin releasing factor, desipramine and haloperidol on a DRL schedule of reinforcement.Pharmacol. Biochem. Behav.,32,967-970.
4. Buhusi, C.V.,Meck, W.H.(2002).Differential effects of methamphetamine and haloperidol on the control of an internal clock.Behav. Neurosci.,116,291-297.
5. Canon, J.G.,Lippa, A.S.(1977).Use of DRL in differentiating anxiolytic and neuroleptic properties of CNS drugs.Pharmacol. Biochem. Behav.,6,591-593.
6. Chang, Y.-H.,Liao, R.-M.,Lan, C.-H.,Sheng, Y.-L.(2000).Tail-Pinch alters operant behavior in the rat: effects of d-amphetamine.Chinese J. Physiol.,43,105-111.
7. Civelli, O.,Bunzow, J.R.,Grandy, D.K.(1993).Molecular diversity of the dopamine receptors.Annu. Rev. Pharmacol. Toxicol.,33,281-307.
8. De Wit, H.,Enggaser, J.L.,Richards, J.B.(2002).Acute administration of d-amphetamine decreases impulsivity in healthy volunteers.Neuropsychopharmacology,27,813-825.
9. Dews, P.B.(1958).Studies on behavior. IV. Stimulant actions of methamphetamine.J. Pharmacol. Exp. Ther.,122,137-147.
10. Drew, M.R.,Fairhurst, S.,Malapani, C.,Horvitz, J.C.,Balsam, P.D.(2003).Effects of dopamine antagonists on the timing of two intervals.Pharmacol. Biochem. Behav.,75,9-15.
11. Feldman, R.S.,Meyer, J.S.,Quenzer, L.F.(1997).Principles of Neuropsychopharmacology.Sunderland, MA:Sinauer Associates.
12. Fowler, S.C.,Liou, J.-R.(1998).Haloperidol, raclopride, and eticlopride induce microcatalepsy during operant performance in rats, but clozapine and SCH23390 do not.Psychopharmacology,140,81-90.
13. Fowler, S.C.,Liou, J.-R.(1994).Microcatalepsy and disruption of forelimb usage during operant behavior: differences between dopamine D1 (SCH-23390) and D2 (raclopride) antagonists.Psychopharmacology,115,24-30.
14. Frederick, D.L.,Allen, J.D.(1996).Effects of selective dopamine D1-and D2-agonists and antagonists on timing performance in rats.Pharmacol. Biochem. Behav.,53,759-764.
15. Gauvin, D.V.,Dormer, K.N.,Holloway, F.A.(1991).Pentylenetetrazole can induce a conditioned place preference.Pharmacol. Biochem. Behav.,40,987-990.
16. Gauvin, D.V.,Holloway, F.A.(1991).Cue dimensionality in the threechoice pentylenetetrazole-saline-chlordiazepoxide discrimination task.Behav. Pharmacol.,2,417-428.
17. Gommans, J.,Hijzen, T.H.,Maes, R.A.A.,Olivier, B.(2000).Discriminative stimulus properties of alprazolam.Psychopharmacology,148,146-152.
18. Grilly, D.M.,Loveland, A.(2001).What is a "low dose" of d-amphetamine for inducing behavioral effects in laboratory rats?.Psychopharmacology,153,155-169.
19. Jung, M.E.,Depoortere, R.,Oglesby, M.W.(2001).Use of negative reinforcing brain stimulation to detect conventional and nonconventional anxiolytics as well as an axiogenic drug.Pharmacol. Biochem. Behav.,68,33-42.
20. Kraemer, P. J.,Randall, C.K.,Dose, J.M.,Brown, R.W.(1997).Impact of d-amphetamine on temporal estimation in pigeons tested with a production procedure.Pharmacol. Biochem. Behav.,58,323-327.
21. Liao, R.-M.,Chang, Y.-H.,Wang, S.-H.(1998).Influence of SCH23390 and spiperone on the expression of conditioned place preference induced by d-amphetamine and cocaine in the rat.Chinese J. Physiol.,41,85-92.
22. Liao, R.-M.,Ko, M.-C.(1995).Chronic effects of haloperidol and SCH23390 on operant and licking behaviors.Chinese J. Physiol.,38,65-73.
23. Liao, R.-M.,Lin, J.-Y.,Cheng, R.-K.,Liao, J.-J.(2001).Effect of SCH23390 and raclopride on a run-climb-run behavioral task in rats.Chinese J. Physiol.,44,151-160.
24. Liester, M.B.,Grob, C.S.,Bravo, G.L.,Walsh, R.N.(1992).Phenomenology and sequelae of 3,4-methylenedioxymethamphetamine use.J. Nerv. Ment. Dise.,180,345-352.
25. Maricq, A.V.,Church, R.M.(1983).The differential effects of haloperidol and methamphetamine on time estimation in the rat.Psychopharmacology,79,10-15.
26. Maricq, A.V.,Roberts, S.,Church, R.M.(1981).Methamphetamine and time estimation.J. Exp. Psychol.: Anim. Behav. Proc.,7,18-30.
27. Mason, S.T.,Beninger, R.J.,Fibiger, H.C.,Phillips, A.G.(1980).Pimozide-induced suppression of responding: evidence against a block of food reward.Pharmacol. Biochem. Behav.,12,917-923.
28. McClure, G.Y.H.,McMillan, D.E.(1997).Effects of drugs on response duration differentiation. VI: differential effects under differential reinforcement of low rates of responding schedules.J. Pharmacol. Exp. Ther.,281,1368-1380.
29. McMillan, D.E.,Wright, D.W.,Wenger, G.R.(1992).Effects of phencyclidine-like drugs on responding under multiple fixed-ratio, fixed-interval schedules.Behav. Pharmacol.,3,143-147.
30. Meck, W.H.(1986).Affinity for the dopamine D2 receptor predicts neuroleptic potency in decreasing the speed of an internal clock.Pharmacol. Biochem. Behav.,25,1185-1189.
31. Meck, W.H.(1996).Neuropharmacology of timing and time perception.Cogn. Brain Res.,3,227-242.
32. Meck, W.H.(1983).Selective adjustment of the speed of internal clock and memory processes.J. Exp. Psychol.: Anim. Behav. Proc.,9,171-201.
33. Meller, E.,Kuga, S.,Friedhoff, A.J.,Goldstein, M.(1985).Selective D2 dopamine receptor agonists prevent catalepsy induced by SCH23390, a selective D1 antagonist.Life Sci.,36,1857-1864.
34. Michaelis, R.C.,Holloway, F.A.,Bird, D.C.,Huerta, P.L.(1987).Interactions between stimulants: effects on DRL performance and lethality in rats.Pharmacol. Biochem. Behav.,27,299-306.
35. Narita, M.,Yoshizawa, K.,Aoki, K.,Takagi, M.,Miyatake, M.,Suzuki, T.(2001).A putative sigma 1 receptor antagonist NE-100 attenuates the discriminative stimulus effects of ketamine in rats.Addic. Biol.,6,373-376.
36. Richards, J.B.,Sabol, K.E.,Seiden, L.E.(1993).DRL interressponsetime distributions: quantification by peak deviation analysis.J. Exp. Anal. Behav.,60,361-368.
37. Rocha, B.A.,Ward, A.S.,Egilmez, Y.,Lytle, D.A.,Emmett-Oglesby, M.W.(1996).Tolerance to the discriminative stimulus and reinforcing effects of ketamine.Behav. Pharmacol.,7,160-168.
38. Sabol, K.E.,Richards, J.B.,Layton, K.,Seiden, L.E.(1995).Amphetamine analogs have differential effects on DRL 36-s schedule performance.Psychopharmacology,121,57-65.
39. Sanger, D.J.(1988).The α2-adrenoceptor antagonists idazoxan and yohimbine increase rat of DRL responding in rats.Psychopharmacology,95,413-417.
40. Sanger, D.J.,Blackman, D.E.(1975).The effects of tranquillizing drugs on timing behavior in rats.Psychopharmacologia (Berl.),44,153-156.
41. Sanger, D.J.,Key, M.,Blackman, D.E.(1974).Differential effects of chlordiazepoxide and d-amphetamine on responding maintained by a DRL schedule of reinforcement.Psychopharmacologia (Berl.),38,159-171.
42. Seiden, L.S.,Sabol, K.E.,Ricaurte, G.A.(1993).Amphetamine: effects on catecholamine systems and behavior.Ann. Rev. Pharmacol. Toxicol.,33,639-677.
43. Senyuz, L.,Fowler, S.C.(1993).Raclopride, but not SCH23390, induces maldirected jumping in rats trained to perform a run-climbrun behavioral task.Psychopharmacology,112,518-520.
44. Sibley, D.R.,Monsma, F.J.,Shen, Y.,Waddington, J. (edited)(1993).D1:D2 Dopamine Receptor Interactions: Neuroscience and Psychopharmacology.London:Academic Press.
45. Sokoloff, P.,Giros, B.,Martres, M.-P.,Bouthenet, M.-L.,Schwartz, J.-C.(1990).Molecular cloning and characterization of a novel dopamine receptor (D3) as a target for neuroleptics.Nature,347,146-151.
46. Spyraki, C.,Fibiger, H.C.,Phillips, A.G.(1982).Dopaminergic substrates of amphetamine-induced place preference conditioning.Brain Res.,253,185-193.
47. Suzuki, T.,Kato, H.,Aoki, T.,Tsuda, M.,Narita, M.,Misawa, M.(2000).Effects of the non-competitive NMDA receptor antagonist ketamine on morphine-induced place preference in mice.Life Sci.,67,383-389.
48. Van Hest, A.,van Drimmelen, M.,Olivier, B.(1992).Flesinoxan shows antidepressant activity in a DRL 72-s screen.Psychopharmacology,107,474-479.
49. Van Hest, A.,van Haaren, F.,van de Poll(1988).N.E. Haloperidol, but not ampomorphine, differentially affects low response rates of male and female Wistar rats.Pharmacol. Biochem. Behav.,29,529-532.
50. Wenger, G.R.,Wright, D.W.(1990).Behavioral effects of cocaine and its interaction with d-amphetamine and morphine in rats.Pharmacol. Biochem. Behav.,35,595-600.
51. Wiley, J.L.,Compton, A.D.,Golden, K.M.(2000).Separation of drug effects on timing and behavioral inhibition by increased stimulus control.Exp. Clin. Psychopharmacol.,8,451-461.

1. Lin, Pu-Hua,Lin, Ching-I,Lin, Chia-Hsien,Chiu, Hui-Fang,Cheng, Jen-Kun,Chen, I-Ming,Chang, Wei-Pin,Chang, Jung-Chen(2014).A Mechanistic Study on Urine Retention in D-Amphetamine Addicts.中國生理學雜誌,57(4),171-181.