Acute effects of d-amphetamine on the differential reinforcement of low-rate (DRL) schedule behavior in the rat: comparison with selective dopamine receptor antagonists.

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]  L. Price,et al.  Phenomenology and sequelae of 3,4-methylenedioxymethamphetamine use , 1992 .

[2]  Bruno Giros,et al.  Molecular cloning and characterization of a novel dopamine receptor (D3) as a target for neuroleptics , 1990, Nature.

[3]  S. Fowler,et al.  Microcatalepsy and disruption of forelimb usage during operant behavior: differences between dopamine D1 (SCH-23390) and D2 (raclopride) antagonists , 1994, Psychopharmacology.

[4]  P. Dews.  Studies on behavior. IV. Stimulant actions of methamphetamine. , 1958, The Journal of pharmacology and experimental therapeutics.

[5]  B. Rocha,et al.  Tolerance to the discriminative stimulus and reinforcing effects of ketamine , 1996, Behavioural pharmacology.

[6]  C. Buhusi,et al.  Differential effects of methamphetamine and haloperidol on the control of an internal clock. , 2002, Behavioral neuroscience.

[7]  D. Sanger.  The α2-adrenoceptor antagonists idazoxan and yohimbine increase rates of DRL responding in rats , 2004, Psychopharmacology.

[8]  S. Fowler,et al.  Haloperidol, raclopride, and eticlopride induce microcatalepsy during operant performance in rats, but clozapine and SCH 23390 do not , 1998, Psychopharmacology.

[9]  D. Grandy,et al.  Molecular diversity of the dopamine receptors. , 1993, Annual review of pharmacology and toxicology.

[10]  A. Friedhoff,et al.  Selective D2 dopamine receptor agonists prevent catalepsy induced by SCH 23390, a selective D1 antagonist. , 1985, Life sciences.

[11]  J. Wiley,et al.  Separation of drug effects on timing and behavioral inhibition by increased stimulus control. , 2000, Experimental and clinical psychopharmacology.

[12]  R M Liao,et al.  Effects of SCH23390 and raclopride on a run-climb-run behavioral task in rats. , 2001, The Chinese journal of physiology.

[13]  S. T. Mason,et al.  Pimozide-induced suppression of responding: Evidence against a block of food reward , 1980, Pharmacology Biochemistry and Behavior.

[14]  D. McMillan,et al.  Effects of drugs on response duration differentiation. VI: differential effects under differential reinforcement of low rates of responding schedules. , 1997, The Journal of pharmacology and experimental therapeutics.

[15]  F. Holloway,et al.  Interactions between stimulants: Effects on DRL performance and lethality in rats , 1987, Pharmacology Biochemistry and Behavior.

[16]  D. Gauvin,et al.  Cue dimensionality in the three-choice pentylenetetrazole-saline-chlordiazepoxide discrimination task. , 1991, Behavioural pharmacology.

[17]  J. Bizot.  Effects of Various Drugs Including Organophosphorus Compounds (OPC) and Therapeutic Compounds Against OPC on DRL Responding , 1998, Pharmacology Biochemistry and Behavior.

[18]  R. Church,et al.  Methamphetamine and time estimation. , 1981, Journal of experimental psychology. Animal behavior processes.

[19]  L S Seiden,et al.  Amphetamine: effects on catecholamine systems and behavior. , 1993, Annual review of pharmacology and toxicology.

[20]  Amphetamine analogs have differential effects on DRL 36-s schedule performance , 1995, Psychopharmacology.

[21]  Warren H. Meck,et al.  Affinity for the dopamine D2 receptor predicts neuroleptic potency in decreasing the speed of an internal clock , 1986, Pharmacology Biochemistry and Behavior.

[22]  M. Narita,et al.  A putative sigma1 receptor antagonist NE‐100 attenuates the discriminative stimulus effects of ketamine in rats , 2001, Addiction biology.

[23]  R. Liao,et al.  Operant performance following tail-pinch in the rat: effects of d-amphetamine. , 2000, The Chinese journal of physiology.

[24]  M. Key,et al.  Differential effects of chlordiazepoxide and d-amphetamine on responding maintained by a DRL schedule of reinforcement , 2004, Psychopharmacologia.

[25]  D. Gauvin,et al.  Pentylenetetrazole can induce a conditioned place preference , 1991, Pharmacology Biochemistry and Behavior.

[26]  Effects of corticotropin releasing factor, desipramine and haloperidol on a DRL schedule of reinforcement , 1989, Pharmacology Biochemistry and Behavior.

[27]  W. Meck.  Selective adjustment of the speed of internal clock and memory processes. , 1983, Journal of experimental psychology. Animal behavior processes.

[28]  J. Richards,et al.  DRL interresponse-time distributions: quantification by peak deviation analysis. , 1993, Journal of the experimental analysis of behavior.

[29]  N. V. Poll,et al.  Haloperidol, but not apomorphine, differentially affects low response rates of male and female wistar rats , 1988, Pharmacology, Biochemistry and Behavior.

[30]  Gauvin Dv,et al.  Cue dimensionality in the three-choice pentylenetetrazole-saline-chlordiazepoxide discrimination task. , 1991 .

[31]  W. Meck.  Neuropharmacology of timing and time perception. , 1996, Brain research. Cognitive brain research.

[32]  D. Sanger,et al.  The effects of tranquillizing drugs on timing behaviour in rats , 1975, Psychopharmacologia.

[33]  M. Tsuda,et al.  Effects of the non-competitive NMDA receptor antagonist ketamine on morphine-induced place preference in mice. , 2000, Life sciences.

[34]  J. Richards,et al.  Sensitization to amphetamine on the differential-reinforcement-of-low-rate 72-s schedule , 1997, Psychopharmacology.

[35]  Raclopride, but not SCH 23390, induces maldirected jumping in rats trained to perform a run-climb-run behavioral task , 2005, Psychopharmacology.

[36]  B. Olivier,et al.  Flesinoxan shows antidepressant activity in a DRL 72-s screen , 2005, Psychopharmacology.

[37]  R. Liao,et al.  Influence of SCH23390 and spiperone on the expression of conditioned place preference induced by d-amphetamine or cocaine in the rat. , 1998, The Chinese journal of physiology.

[38]  D. M. Grilly,et al.  What is a "low dose" of d-amphetamine for inducing behavioral effects in laboratory rats? , 2000, Psychopharmacology.

[39]  Joseph D. Allen,et al.  Effects of selective dopamine D1- and D2-agonists and antagonists on timing performance in rats , 1996, Pharmacology Biochemistry and Behavior.

[40]  J. Horvitz,et al.  Effects of dopamine antagonists on the timing of two intervals , 2003, Pharmacology Biochemistry and Behavior.

[41]  A. Lippa,et al.  Use of DRL in differentiating anxiolytic and neuroleptic properties of CNS drugs , 1977, Pharmacology Biochemistry and Behavior.

[42]  J. Richards,et al.  Acute Administration of d-Amphetamine Decreases Impulsivity in Healthy Volunteers , 2002, Neuropsychopharmacology.

[43]  M. Tsuda,et al.  Effects of the non-competitive NMDA receptor antagonist ifenprodil on the morphine-induced place preference in mice. , 1999, Life sciences.

[44]  R. Church,et al.  The differential effects of haloperidol and methamphetamine on time estimation in the rat , 2004, Psychopharmacology.

[45]  R. Depoortère,et al.  Use of negatively reinforcing electrical brain stimulation to detect conventional and nonconventional anxiolytics as well as an anxiogenic drug , 2001, Pharmacology Biochemistry and Behavior.

[46]  Jerrold S. Meyer,et al.  Principles of Neuropsychopharmacology , 1997 .

[47]  G. Wenger,et al.  Behavioral effects of cocaine and its interaction with d-amphetamine and morphine in rats , 1990, Pharmacology Biochemistry and Behavior.

[48]  A. Phillips,et al.  Dopaminergic substrates of amphetamine-induced place preference conditioning , 1982, Brain Research.

[49]  Impact of d-Amphetamine on Temporal Estimation in Pigeons Tested with a Production Procedure , 1997, Pharmacology Biochemistry and Behavior.